Cell and Tissue Research

, Volume 343, Issue 2, pp 263–287 | Cite as

Channels and transporters in salivary glands

  • Eleni RoussaEmail author


According to the two-stage hypothesis, primary saliva, a NaCl-rich plasma-like isotonic fluid is secreted by salivary acinar cells and its ionic composition becomes modified in the duct sytem. The ducts secrete K+ and HCO 3 - and reabsorb Na+ and Cl- without any water movement, thus establishing a hypotonic final saliva. Salivary secretion depends on the coordinated action of several channels and transporters localized in the apical and basolateral membrane of acinar and duct cells. Early functional studies in perfused glands, followed by the molecular cloning of several transport proteins and the subsequent analysis of mutant mice, have greatly contributed to our understanding of salivary fluid and the electrolyte secretion process. With a few exceptions, most of the key channels and transporters involved in salivary secretion have now been identified and characterized. However, the picture that has emerged from all these studies is one of a complex molecular network characterized by redundancy for several transport proteins, compensatory mechanisms, and adaptive changes in health and disease. Current research is directed to the molecular interactions between the determinants and the ways in which they are regulated by extracellular signals and intracellular mediators. This review focuses on the functionally and molecularly best-characterized channels and transporters that are considered to be involved in transepithelial fluid and electrolyte transport in salivary glands.


Salivary gland Submandibular Parotid Acid-base transport Chloride transport Potassium transport Mammals 



The author acknowledges the valuable contributions made by past and present collaborators and by members of her laboratory. She thanks Cornelius Schlosshardt for Figs. 1 and 2.


  1. Akamatsu T, Parvin MN, Murdiastuti K, Kosugi-Tanaka C, Yao C, Miki O, Kanamori N, Hosoi K (2003) Expression and localization of aquaporins, members of the water channel family, during development of the rat submandibular gland. Pflugers Arch 446:641–651PubMedCrossRefGoogle Scholar
  2. Alper SL (1994) The band 3-related AE anion exchanger gene family. Cell Physiol Biochem 4:265–281CrossRefGoogle Scholar
  3. Alper SL (2002) Genetic diseases of acid-base transporters. Annu Rev Physiol 64:899–923PubMedCrossRefGoogle Scholar
  4. Alper SL, Kopito RR, Libresco SM, Lodish HF (1988) Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line. J Biol Chem 263:17092–17099PubMedGoogle Scholar
  5. Alper SL, Natale J, Gluck S, Lodish HF, Brown D (1989) Subtypes of intercalated cells in rat kidney collecting duct defined by antibodies against erythroid band 3 and renal vacuolar H+-ATPase. Proc Natl Acad Sci USA 86:5429–5433PubMedCrossRefGoogle Scholar
  6. Arreola J, Melvin JE, Begenisich T (1995) Volume-activated chloride channels in rat parotid acinar cells. J Physiol (Lond) 484:677–687Google Scholar
  7. Arreola J, Park K, Melvin JE, Begenisich T (1996) Three distinct chloride channels control anion movements in rat parotid acinar cells. J Physiol (Lond) 490:351–362Google Scholar
  8. Arreola J, Begenisich T, Nehrke K, Nguyen HV, Park K, Richardson L, Yang B, Schutte BC, Lamb FS, Melvin JE (2002) Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene. J Physiol (Lond) 545:207–216CrossRefGoogle Scholar
  9. Augustus J (1976) Evidence for electrogenic sodium pumping in the ductal epithelium of rabbit salivary gland and its relationship with Na-K-ATPase. Biochim Biophys Acta 419:63–75PubMedCrossRefGoogle Scholar
  10. Begenisich T, Nakamoto T, Ovitt CE, Nehrke K, Brugnara C, Alper SL, Melvin JE (2004) Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4. J Biol Chem 279:47681–47687PubMedCrossRefGoogle Scholar
  11. Beroukas D, Hiscock J, Jonsson R, Waterman SA, Gordon TP (2001) Subcellular distribution of aquaporin-5 in salivary glands in primary Sjögren syndrome. Lancet 358:1875–1876PubMedCrossRefGoogle Scholar
  12. Beroukas D, Hiscock J, Gannon BJ, Jonsson R, Gordon TP, Wateman SA (2002) Selective down-regulation of aquaporin-1 in salivary glands in primary Sjögren syndrome. Lab Invest 82:1547–1552PubMedGoogle Scholar
  13. Best JA, Quinton PM (2005) Salivary secretion assay for drug efficacy for cystic fibrosis in mice. Exp Physiol 90:189–193PubMedCrossRefGoogle Scholar
  14. Blair HC, Teitelbaum SL, Ghiselli R, Gluck S (1989) Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 245:855–857PubMedCrossRefGoogle Scholar
  15. Bok D, Schibler MJ, Pushkin A, Sassani P, Abuladze N, Naser Z, Kurtz I (2001) Immunolocalization of electrogenic sodiumbicarbonate cotransporters pNBC1 and kNBC1 in the rat eye. Am J Physiol Renal Physiol 281:F920–F935PubMedGoogle Scholar
  16. Boron WF, Boulpaep EL (1983) Intracellular pH regulation in the renal proximal tubule of the salamander: basolateral HCO3- transport. J Gen Physiol 81:53–94PubMedCrossRefGoogle Scholar
  17. Brandes A, Oehlke O, Schümann A, Heidrich S, Thévenod F, Roussa E (2007) Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances. Am J Physiol Regul Integr Comp Physiol 293:R2400–R2411PubMedGoogle Scholar
  18. Breton S, Brown D (2007) New insights into the regulation of V-ATPase-dependent proton secretion. Am J Physiol Renal Physiol 292:F1–F10PubMedCrossRefGoogle Scholar
  19. Breton S, Smith P, Lui B, Brown D (1996) Acidification of the male reproductive tract by a proton pumping H+ ATPase. Nat Med 2:470–472PubMedCrossRefGoogle Scholar
  20. Brown D, Hirsch S, Gluck S (1988) An H+-ATPase in opposite plasma membrane domains in kidney epithelial cell subpopulations. Nature 331:622–624PubMedCrossRefGoogle Scholar
  21. Brown PD, Elliot AC, Lau KR (1989) Indirect evidence for the presence of non-specific anion channels in rabbit mandibular salivary gland acinar cells. J Physiol (Lond) 414:415–431Google Scholar
  22. Brown D, Breton S, Ausiello DA, Marshansky V (2009) Sensing, signaling and sorting events in kidney epithelial cell physiology. Traffic 10:275–284PubMedCrossRefGoogle Scholar
  23. Brugnara C (1993) Membrane transport of Na and K and cell dehydration in sickle erythrocytes. Experientia 49:100–109PubMedCrossRefGoogle Scholar
  24. Brugnara C, Tosteson DC (1987) Cell volume, K+ transport, and cell density in human erythrocytes. Am J Physiol 252:C269–C276PubMedGoogle Scholar
  25. Burgoyne RD, Morgan A (2003) Secretory granule exocytosis. Physiol Rev 83:581–632PubMedGoogle Scholar
  26. Butterworth MB, Edinger RS, Frizzell RA, Johnson JP (2009) Regulation of the epithelial sodium channel by membrane trafficking. Am J Physiol Renal Physiol 296:F10–F24PubMedCrossRefGoogle Scholar
  27. Canessa CM, Schild D, Buell G, Thorens B, Gautschi I, Horisberger JD, Rossier BC (1994) Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 367:463–467PubMedCrossRefGoogle Scholar
  28. Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322:590–594PubMedCrossRefGoogle Scholar
  29. Catalan MA, Nakamoto T, Ganzalez-Begne M, Camden JM, Wall SM, Clarke LL, Melvin JE (2010) Cftr and ENaC ion channels mediate NaCl reabsorption in the mouse submandibular gland. J Physiol (Lond) 588:713–724CrossRefGoogle Scholar
  30. Chaturapanich G, Ishibashi H, Dinudom A, Young JA, Cook DI (1997) H+ transporters in the main excretory duct of the mouse mandibular salivary gland. J Physiol (Lond) 503:583–598CrossRefGoogle Scholar
  31. Compton J, Martinez JR, Martinez AM, Young JA (1981) Fluid and electrolyte secretion from the isolated, perused submandibular and sublingual glands of the rat. Arch Oral Biol 26:555–561PubMedCrossRefGoogle Scholar
  32. Cook DI, Van Lennep EW, Roberts ML, Young J (1994) Secretion by the major salivary glands. In: Johnson L, Christensen J, Jackson M, Jacobson E, Walsh J (eds) Physiology of the gastrointestinal tract. Raven, New York, pp 1061–1117Google Scholar
  33. Cook DI, Dinudom A, Komwatana P, Young JA (1998) Control of Na+ transport in salivary duct epithelial cells by cytosolic Cl- and Na+. Eur J Morphol 36 (Suppl):67–73PubMedGoogle Scholar
  34. Cook DI, Dinudom A, Komwatana P, Kumar S, Young JA (2002) Patch-clamp studies on epithelial sodium channels in salivary duct cells. Cell Biochem Biophys 36:105–113PubMedCrossRefGoogle Scholar
  35. Cutler LS, Chaudhry AP (1973) Release and restoration of the secretory granules in the convoluted granular tubules of the rat submandibular gland. Anat Rec 176:405–420PubMedCrossRefGoogle Scholar
  36. Da Silva N, Pisitkun T, Belleannée C, Miller LR, Nelson R, Knepper MA, Brown D, Breton S (2010) Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence-activated cell sorting. Am J Physiol Cell Physiol 298:C1326–C1342PubMedCrossRefGoogle Scholar
  37. Damkier HH, Nielsen S, Praetorius J (2007) Molecular expression of SLC4-derived Na+-dependent anion transporters in selected human tissues. Am J Physiol Regul Integr Comp Physiol 293:R2136–R2246PubMedGoogle Scholar
  38. De Camilli P, Peluchetti D, Meldolesi J (1976) Dynamic changes of the luminal plasmalemma in stimulated parotid acinar cells. A freeze-fracture study. J Cell Biol 701:59–74CrossRefGoogle Scholar
  39. Dehaye JP, Turner RJ (1991) Isolation and characterization of rat submandibular intralobular ducts. Am J Physiol 261:C490–C496PubMedGoogle Scholar
  40. Delporte C, Steinfeld S (2006) Distribution and roles of aquaporins in salivary glands. Biochim Biophys Acta 1758:1061–1070PubMedCrossRefGoogle Scholar
  41. Denniss AR, Young JA (1978) Modification of salivary duct electrolyte transport in rat and rabbit by physalaemin, VIP, GIP and other enterohormones. Pflugers Arch 376:73–80PubMedCrossRefGoogle Scholar
  42. Dinour D, Chang MH, Satoh JI, Smith BL, Angle N, Knecht A, Serban I, Holtzman EJ, Romero MF (2004) A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. J Biol Chem 279:52238–52246PubMedCrossRefGoogle Scholar
  43. Dinudom A, Young JA, Cook DI (1993a) Amiloride-sensitive Na+ current in the granular duct cells of mouse mandibular glands. Pflugers Arch 423:164–166PubMedCrossRefGoogle Scholar
  44. Dinudom A, Young JA, Cook DI (1993b) Na+ and Cl- conductances are controlled by cytosolic Cl- concentration in the intralobular duct cells of mouse mandibular glands. J Membr Biol 135:289–295PubMedGoogle Scholar
  45. Dinudom A, Young JA, Cook DI (1994) Ion channels in the basolateral membrane of intralobular duct cells of mouse mandibular glands. Pflugers Arch 428:202–208PubMedCrossRefGoogle Scholar
  46. Dinudom A, Komwatana P, Young JA, Cook DI (1995) A forskolin-activated Cl- current in mouse mandibular duct cells. Am J Physiol 268:G806–G812PubMedGoogle Scholar
  47. Dissing S, Nauntofte B (1990) Na+ transport properties of isolated rat parotid acini. Am J Physiol 259:G1044–G1055PubMedGoogle Scholar
  48. Dorey G, Bhoola KD (1972) II. Ultrastructure of duct cell granules in mammalian submaxillary glands. Z Zellforsch 126:335–347PubMedCrossRefGoogle Scholar
  49. Drenckhahn D, Schluter K, Allen DP, Bennet V (1985) Colocalization of band 3 with ankyrin and spectrin at the basal membrane of intercalated cells in the rat kidney. Science 230:1287–1289PubMedCrossRefGoogle Scholar
  50. Eladari D, Leviel F, Pezy F, Paillard M, Chambrey R (2002) Rat proximal NHE3 adapts to chronic acid-base disorders but not to chronic changes in dietary NaCl intake. Am J Physiol Renal Physiol 282:F835–F843PubMedGoogle Scholar
  51. Elkjaer ML, Nejsum LN, Gresz V, Kwon TH, Jensen UB, Frøkiaer J, Nielsen S (2001) Immunolocalization of aquaporin-8 in rat kidney, gastrointestinal tract, testis, and airways. Am J Physiol Renal Physiol 281:F1047–F1057PubMedGoogle Scholar
  52. Endo Y, Yamazaki S, Moriyama N, Li Y, Ariizumi T, Kudo A, Kawakami H, Tanaka Y, Horita S, Yamada H, Seki G, Fujita T (2006) Localization of NBC1 variants in rat kidney. Nephron Physiol 104:87–94CrossRefGoogle Scholar
  53. Evans RL, Lau KR, Case RM (1993) Structural and functional characterization of striated ducts isolated from the rabbit mandibular salivary gland. Exp Physiol 78:49–64PubMedGoogle Scholar
  54. Evans RL, Bell SM, Schultheis PJ, Shull GE, Melvin JE (1999) Targeted disruption of the Nhe1 gene prevents muscarinic agonist-induced up-regulation of Na+-H+ exchange in mouse parotid acinar cells. J Biol Chem 274:29025–29030PubMedCrossRefGoogle Scholar
  55. Evans RL, Park K, Turner RJ, Watson GE, Ngyen HV, Denett MR, Hand AR, Flagella M, Shull GE, Melvin JE (2000) Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. J Biol Chem 275:26720–26726PubMedGoogle Scholar
  56. Field MJ, Young JA (1973) Kinetics of Na+ transport in the rat submaxillary main duct perfused in vitro. Pflugers Arch 345:207–220PubMedCrossRefGoogle Scholar
  57. Finbow ME, Harrison MA (1997) The vacuolar H+-ATPase: a universal proton pump of eukaryotes. Biochem J 324:697–712PubMedGoogle Scholar
  58. Flon H, Gerstner R, Mitchell OG, Feldman A (1970) Salivary glands of heteromyid rodents with a summary of the literature on rodent submandibular gland morphology. J Morphol 131:179–194PubMedCrossRefGoogle Scholar
  59. Foskett JK, Gunter-Smith PJ, Melvin JE, Turner RJ (1989) Physiological localization of an agonist-sensitive pool of Ca2+ in parotid acinar cells. Proc Natl Acad Sci USA 86:167–171PubMedCrossRefGoogle Scholar
  60. Frigeri A, Gropper MA, Umenishi F, Kawashima M, Brown D, Verkman AS (1995) Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues. J Cell Sci 108:2993–3002PubMedGoogle Scholar
  61. Funaki H, Yamamoto T, Koyama Y, Kondo D, Yaoita E, Kawasaki K, Kobayashi H, Sawaguchi S, Abe H, Kihara I (1998) Localization and expression of AQP5 in cornea, serous salivary glands, and pulmonary epithelial cells. Am J Physiol 275:C1151–C1157PubMedGoogle Scholar
  62. Gallacher DV, Morris AP (1986) A patch-clamp study of potassium currents in resting and acetylcholine-stimulated mouse submandibular acinar cells. J Physiol (Lond) 373:379–395Google Scholar
  63. Gamba G (2005) Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev 85:423–493PubMedCrossRefGoogle Scholar
  64. Gawenis LR, Ledoussal C, Judd LM, Prasad V, Alper SL, Stuart-Tilley A, Woo AL, Grisham C, Sanford LP, Doetschman T, Miller ML, Shull GE (2004) Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. J Biol Chem 279:30531–30539PubMedCrossRefGoogle Scholar
  65. Gawenis LR, Bradford EM, Prasad V, Lorenz JN, Simpson JE, Clarke LL, Woo AL, Grisham C, Sanford LP, Doetschman T, Miller ML, Shull GE (2007) Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. J Biol Chem 282:9042–9052PubMedCrossRefGoogle Scholar
  66. Gillen CM, Brill S, Payne JA, Forbush B (1996) Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. J Biol Chem 27:16237–16244Google Scholar
  67. Gonzalez-Begne M, Nakamoto T, Nguyen HV, Stewart AK, Alper SL, Melvin JE (2007) Enhanced formation of a HCO3- transport metabolon in exocrine cells of Nhe1-/- mice. J Biol Chem 282:35125–35132PubMedCrossRefGoogle Scholar
  68. Greeley T, Shumaker H, Wang Z, Schweinfest CW, Soleimani M (2001) Downregulated in adenoma and putative anion transporter are regulated by CFTR in cultured pancreatic duct cells. Am J Physiol 281:G1301–G1308Google Scholar
  69. Gresz V, Kwon TH, Hurley PT, Varga G, Zelles T, Nielsen S, Case RM, Steward MC (2001) Identification and localization of aquaporin water channels in human salivary glands. Am J Physiol Gastrointest Liver Physiol 281:G247–G254PubMedGoogle Scholar
  70. Gresz V, Kwon TH, Vorum H, Zelles T, Kurtz I, Steward MC, Aalkjaer C, Nielsen S (2002) Immunolocalization of electroneutral Na+-HCO3- cotransporters in human and rat salivary glands. Am J Physiol Gastrointest Liver Physiol 283:G473–G480PubMedGoogle Scholar
  71. Grichtchenko II, Choi I, Zhong X, Bray-Ward P, Russell JM, Boron WF (2001) Cloning, characterization, and chromosomal mapping of a human electroneutral Na+-driven Cl-/HCO3- exchanger. J Biol Chem 276:8358–8363PubMedCrossRefGoogle Scholar
  72. Haas M, Forbush B (2000) The Na-K-Cl cotransport of secretory epithelia. Annu Rev Physiol 62:515–534PubMedCrossRefGoogle Scholar
  73. Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS (1994) Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. J Biol Chem 269:5497–5500PubMedGoogle Scholar
  74. Hayashi T, Young JA, Cook DI (1996) The ACh-evoked Ca2+-activated K+ current in mouse mandibular secretory cells. Single channel studies. J Membr Biol 151:19–27PubMedCrossRefGoogle Scholar
  75. Hayashi M, Komazaki S, Ishikawa T (2003) An inwardly rectifying K+ channel in bovine parotid acinar cells: possible involvement of Kir2.1. J Physiol (Lond) 547:255–269CrossRefGoogle Scholar
  76. He X, Tse CM, Donowitz M, Alper SL, Gabriel SE, Baum BJ (1997) Polarized distribution of key membrane transport proteins in the rat submandibular gland. Pflugers Arch 433:3268–3273Google Scholar
  77. Hiki K, D’Andrea RJ, Furze J, Crawford J, Woollatt E, Sutherland GR, Vadas MA, Gamble JR (1999) Cloning, characterization, and chromosomal location of a novel K+-Cl- cotransporter. J Biol Chem 274:10661–10667PubMedCrossRefGoogle Scholar
  78. Hiratsuka K, Kamino Y, Nagata T, Takahashi Y, Asai S, Ishikawa K, Abiko Y (2002) Microarray analysis of gene expression changes in aging in mouse submandibular gland. J Dent Res 81:679–682PubMedCrossRefGoogle Scholar
  79. Holtzman EJ, Kumar S, Faaland CA, Warner F, Logue PJ, Erickson SJ, Ricken G, Waldman J, Kumar S, Dunham PB (1998) Cloning, characterization, and gene organization of K-Cl cotransporter from pig and human kidney and C. elegans. Am J Physiol 275:F550–F564PubMedGoogle Scholar
  80. Homann V, Rosin-Steiner S, Stratmann T, Arnold WH, Gaengler P, Kinne RK (2005) Sodium-phosphate cotransporter in human salivary glands: molecular evidence for the involvement of NPT2b in acinar phosphate secretion and ductal phosphate reabsorption. Arch Oral Biol 50:759–768PubMedCrossRefGoogle Scholar
  81. Horita S, Yamada H, Inatomi J, Moriyama N, Sekine T, Igarashi T, Endo Y, Dasouki M, Ekim M, Al-Gazali L, Shimadzu M, Seki G, Fujita T (2005) Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities. J Am Soc Nephrol 16:2270–2278PubMedCrossRefGoogle Scholar
  82. Igarashi T, Inatomi J, Sekine T, Cha SH, Kanai Y, Kunimi M, Tsukamoto K, Satoh H, Shimadzu M, Tozawa F, Mori T, Shiobara M, Seki G, Endou H (1999) Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat Genet 23:264–266PubMedCrossRefGoogle Scholar
  83. Ishibashi K, Yamazaki J, Okamura K, Teng Y, Kitamura K, Abe K (2006) Roles of CLCA and CFTR in electrolyte re-absorption from rat saliva. J Dent Res 85:1101–1105PubMedCrossRefGoogle Scholar
  84. Ishibashi K, Okamura K, Yamazaki J (2008) Involvement of apical P2Y2 receptor-regulated CFTR activity in muscarinic stimulation of Cl- reabsorption in rat submandibular gland. Am J Physiol Regul Integr Comp Physiol 294:R1729–R1736PubMedGoogle Scholar
  85. Ishikawa Y, Yuan Z, Inoue N, Skowronski MT, Nakae Y, Shono M, Cho G, Yasui M, Agre P, Nielsen S (2005) Identification of AQP5 in lipid rafts and its translocation to apical membranes by activation of M3 mAChRs in interlobular ducts of rat parotid gland. Am J Physiol Cell Physiol 289:C1303–C1311PubMedCrossRefGoogle Scholar
  86. Iwano T, Akayama M, Yamamoto A, Omori K, Kumazawa T, Tashiro Y (1987) Quantitative immunoelectron microscopic localization of Na+, K+-ATPase in rat parotid gland. J Histochem Cytochem 35:871–880PubMedGoogle Scholar
  87. Iwatsuki N, Maruyama Y, Matsumoto O, Nishiyama A (1985) Activation of Ca2+-dependent Cl- and K+ conductances in rat and mouse acinar cells. Jpn J Physiol 35:933–944PubMedCrossRefGoogle Scholar
  88. Jensen BS, Strobaek D, Christophersen P, Jorgensen TD, Hansen C, Silahtaroglu A, Olesen SP, Ahring PK (1998) Characterization of the cloned human intermediate-conductance Ca2+-activated K+ channel. Am J Physiol Cell Physiol 275:C848–C856Google Scholar
  89. Jhiang SM, Cho JY, Ryu KY, DeYoung BR, Smanik PA, McGaughy VR, Fischer AH, Mazzaferri EL (1998) An immunohistochemical study of Na+/I- symporter in human thyroid tissues and salivary gland tissues. Endocrinology 39:4416–4419CrossRefGoogle Scholar
  90. Jirakulsomchok D, Schneyer CA (1984) Effects of adrenergic agonists on electrolyte transport in perfused salivary duct of rat. J Auton Nerv Syst 11:233–241PubMedCrossRefGoogle Scholar
  91. Jirakulsomchok D, Schneyer CA (1987) Effects of sympathetic nerve stimulation in the presence of specific adrenergic antagonists on Na+, K+, and Cl- transport in perfused rat submandibular duct. J Auton Nerv Syst 19:255–259PubMedCrossRefGoogle Scholar
  92. Josephsen K, Praetorius J, Frische S, Gawenis LR, Kwon TH, Agre P, Nielsen S, Fejerskov O (2009) Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in mice. Proc Natl Acad Sci USA 106:1638–1641PubMedCrossRefGoogle Scholar
  93. Kawedia JD, Nieman ML, Boivin GP, Melvin JE, Kikuchi K, Hand AR, Lorenz JN, Menon AG (2007) Interaction between transcellular and paracellular water transport pathways through aquaporin 5 and the tight junction complex. Proc Natl Acad Sci USA 104:3621–3626PubMedCrossRefGoogle Scholar
  94. Kim YB, Yang BH, Piao ZG, Oh SB, Kim JS, Park K (2003) Expression of Na+/HCO3- cotransporter and its role in pH regulation in mouse parotid acinar cells. Biochem Biophys Res Commun 304:593–598PubMedCrossRefGoogle Scholar
  95. King LS, Nielsen S, Agre P (1997) Aquaporins in complex tissues. I. Developmental patterns in respiratory and glandular tissues of rat. Am J Physiol 273:C1541–C1548PubMedGoogle Scholar
  96. Klanke CA, Su YR, Callen DF, Wang Z, Meneton P, Baird N, Kandasamy RA, Orlowski J, Otterud BE, Leppert M, et al (1995) Molecular cloning and physical and genetic mapping of a novel human Na+/H+ exchanger (NHE5/SLC9A5) to chromosome 16q22.1. Genomics 25:615–622PubMedCrossRefGoogle Scholar
  97. Knauf H (1972) The minimum requirements for the maintenance of active sodium transport across the isolated salivary duct epithelium of the rabbit. Pflugers Arch 333:326–336PubMedCrossRefGoogle Scholar
  98. Knauf H, Röttger P, Wais U, Baumann K (1975) On the regulatory handling of Na+, K+ and H+ transport by the rat salivary epithelium. Fortschr Zool 23:307–321PubMedGoogle Scholar
  99. Knauf H, Lubcke R, Kreutz W, Sachs W (1982) Interrelationships of ion transport in rat submaxillary duct epithelium. Am J Physiol 242:F132–F139PubMedGoogle Scholar
  100. Ko SB, Luo X, Hager H, Rojek A, Choi JY, Licht C, Suzuki M, Muallem S, Nielsen S, Ishibashi K (2002) AE4 is a DIDS-sensitive Cl-/HCO3- exchanger in the basolateral membrane of the renal CCD and the SMG duct. Am J Physiol 283:C1206–C1218Google Scholar
  101. Komwatana P, Dinudom A, Young JA, Cook DI (1996) Control of the amiloride-sensitive Na+ current in salivary duct cells by extracellular sodium. J Membr Biol 150:133–141PubMedCrossRefGoogle Scholar
  102. Koo NY, Li J, Hwang SM, Choi SY, Lee SJ, Oh SB, Kim JS, Lee JH, Park K (2006) Molecualr cloning and functional expression of a sodium bicarbonate cotransporter from guinea-pig parotid glands. Biochem Biophys Res Commun 342:1114–1122PubMedCrossRefGoogle Scholar
  103. Kopito RR, Lee BS, Simmons DM, Lindsey AE, Morgens CW, Schneider K (1989) Regulation of intracellular pH by a neuronal homolog of the erythrocyte anion exchanger. Cell 59:927–937PubMedCrossRefGoogle Scholar
  104. Krane CM, Melvin JE, Nguyen HV, Richardson L, Towne JE, Doetschman T, Menon AG (2001) Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane water permeability and altered cell volume regulation. J Biol Chem 276:23413–23420PubMedCrossRefGoogle Scholar
  105. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, Haussinger D (1998) Functional significance of cell volume regulatory mechanisms. Physiol Rev 78:247–306PubMedGoogle Scholar
  106. Larsen HS, Ruus AK, Galtung HK (2009) Aquaporin expression patterns in the developing mouse salivary gland. Eur J Oral Sci 117:655–662PubMedCrossRefGoogle Scholar
  107. Larsen HS, Ruus A-K, Schreurs O, Galtung HK (2010) Aquaporin 11 in the developing mouse submandibular gland. Eur J Oral Sci 118:9–13PubMedCrossRefGoogle Scholar
  108. Lau KR, Elliott AC, Brown PD (1989) Acetylcholine-induced intracellular acidosis in rabbit salivary gland acinar cells. Am J Physiol 256:C288–C295PubMedGoogle Scholar
  109. Lau KR, Evans RL, Case RM (1994) Intracellular Cl- concentration in striated intralobular ducts from rabbit mandibular salivary glands. Pflugers Arch 427:24–32PubMedCrossRefGoogle Scholar
  110. Lauf PK, Adragna NC (2000) K-Cl cotransport: properties and molecular mechanism. Cell Physiol Biochem 10:341–354PubMedCrossRefGoogle Scholar
  111. Lee MG, Schultheis PJ, Yan M, Shull GE, Bookstein C, Chang E, Tse M, Donowitz M, Park K, Muallem S (1998) Membrane-limited expression and regulation of Na+-H+ exchanger isoforms by P2 receptors in the rat submandibular gland duct. J Physiol (Lond) 513:341–357CrossRefGoogle Scholar
  112. Lee BS, Gluck SL, Holiday IS (1999a) Interaction between vacuolar H+-ATPase and microfilaments during osteoclast activation. J Biol Chem 274:29164–29171PubMedCrossRefGoogle Scholar
  113. Lee MG, Choi JY, Luo X, Strickland E, Thomas PJ, Muallem S (1999b) Cystic fibrosis transmembrane conductance regulator regulates luminal Cl-/HCO3- exchange in mouse submandibular and pancreatic ducts. J Biol Chem 274:14670–14677PubMedCrossRefGoogle Scholar
  114. Leviel F, Hübner CA, Houillier P, Morla L, El Moghrabi S, Brideau G, Hatim H, Parker MD, Kurth I, Kougioumtzes A, Sinning A, Pech V, Riemondy KA, Miller RL, Hummler E, Shull GE, Aronson PS, Doucet A, Wall SM, Chambrey R, Eladari D (2010) The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. J Clin Invest 120:1627–1635PubMedCrossRefGoogle Scholar
  115. Li J, Ha YM, Kü NY, Choi SY, Lee SJ, Oh SB, Kim JS, Lee JH, Lee EB, Song YW, Park K (2004) Inhibitory effects of autoantibodies on the muscarinic receptors in Sjögren’s syndrome. Lab Invest 84:1430–1438PubMedCrossRefGoogle Scholar
  116. Li J, Koo NY, Cho IH, Kwon TH, Choi SY, Lee SJ, Oh SB, Kim JS, Park K (2006) Expression of the Na+-HCO3- cotransporter and its role in pHi regulation in guinea pig salivary glands. Am J Physiol Gastrointest Liver Physiol 291:G1031–G1040PubMedCrossRefGoogle Scholar
  117. Luo X, Choi JY, Ko SB, Pushkin A, Kurtz I, Ahn W, Lee MG, Muallem S (2001) HCO3- salvage mechanism in the submandibular gland acinar and duct cells. J Biol Chem 30:9808–9816CrossRefGoogle Scholar
  118. Ma T, Song Y, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (1999) Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels. J Biol Chem 274:20071–20074PubMedCrossRefGoogle Scholar
  119. Majid A, Brown PD, Best L, Park K (2001) Expression of volume-sensitive Cl- channels and ClC-3 in acinar cells isolated from the rat lacrimal and submandibular salivary gland. J Physiol (Lond) 534:409–421CrossRefGoogle Scholar
  120. Manganel R, Turner RJ (1988) Na+/H+ exchange in rat parotid basolateral membrane vesicles. J Membr Biol 102:247–254PubMedCrossRefGoogle Scholar
  121. Marshansky V, Futai M (2008) The V-type H+-ATPase in vesicular trafficking: targeting, regulation and function. Curr Opin Cell Biol 20:415–426PubMedCrossRefGoogle Scholar
  122. Martinez JR, Cassity N (1983) Effect of transport inhibitors on secretion by perfused rat submandibular gland. Am J Physiol 245:G711–G716PubMedGoogle Scholar
  123. Martinez JR, Cassity N (1985) Cl- requirement for saliva secretion in the isolated, perused rat submandibular gland. Am J Physiol 249:G464–G469PubMedGoogle Scholar
  124. Martinez JR, Cassity N (1986) 36Cl fluxes in dispersed rat submandibular acini: effects of Ca2+ omission and of the ionophore A23187. Pflugers Arch 407:615–619PubMedCrossRefGoogle Scholar
  125. Martinez JR, Holzgreve H, Frick A (1966) Micropuncture study of submaxillary glands of adult rats. Pflugers Arch Gesamte Physiol Menschen Tiere 290:124–133PubMedCrossRefGoogle Scholar
  126. Maruyama Y, Gallacher DV, Petersen OH (1983) Voltage and Ca2+-activated K+ channel in basolateral acinar cell membranes of mammalian salivary glands. Nature 302:827–829PubMedCrossRefGoogle Scholar
  127. Maruyama Y, Nishiyama A, Izumi T, Hoshimiya N, Petersen OH (1986) Ensemble noise and current relaxation analysis of K+ current in single isolated salivary acinar cells from rat. Pflugers Arch 406:69–72PubMedCrossRefGoogle Scholar
  128. Matsuzaki T, Suzuki T, Koyama H, Tanaka S, Takata K (1999) Aquaporin-5 (AQP5), a water channel protein, in the rat salivary and lacrimal glands: immunolocalization and effect of secretory stimulation. Cell Tissue Res 295:513–521PubMedCrossRefGoogle Scholar
  129. Melvin JE, Turner RJ (1992) Cl- fluxes related to fluid secretion by the rat parotid: involvement of Cl-/HCO3- exchange. Am J Physiol 262:G393–G398PubMedGoogle Scholar
  130. Melvin JE, Kawaguchi M, Baum BJ, Turner RJ (1987) A muscarinic agonist-stimulated chloride efflux pathway is associated with fluid secretion in rat parotid acinar cells. Biochem Biophys Res Commun 145:754–759PubMedCrossRefGoogle Scholar
  131. Melvin JE, Moran A, Turner RJ (1988) The role of HCO3- and Na+/H+ exchange in the response of rat parotid and acinar cells to muscarinic stimulation. J Biol Chem 263:19564–19569PubMedGoogle Scholar
  132. Mercado A, Song L, Vázquez N, Mount DB, Gamba G (2000) Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4. J Biol Chem 275:30326–30334PubMedCrossRefGoogle Scholar
  133. Mount DB, Hoover RS, Hebert SC (1997) The molecular physiology of electroneutral cation-chloride cotransport. J Membr Biol 158:177–186PubMedCrossRefGoogle Scholar
  134. Mount DB, Mercado A, Song L, Xu J, Georg AL Jr, Delpire E, Gamba G (1999) Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family. J Biol Chem 274:16355–16362PubMedCrossRefGoogle Scholar
  135. Murakami M, Miyamoto S, Imai Y (1990) Oxygen consumption for K+ uptake during post-stimulatory activation of Na+, K+-ATPase in perfused rat mandibular gland. J Physiol (Lond) 426:127–143Google Scholar
  136. Murakami M, Shachar-Hill B, Steward MC, Hill AE (2001) The paracellular component of water flow in the rat submandibular salivary gland. J Physiol (Lond) 537:899–906CrossRefGoogle Scholar
  137. Murakami M, Murdiastuti K, Hosoi K, Hill AE (2006) AQP and the control of fluid transport in a salivary gland. J Membr Biol 210:91–103PubMedCrossRefGoogle Scholar
  138. Murdiastuti K, Miki O, Yao C, Parvin MN, Kosugi-Tanaka C, Akamatsu T, Kanamori N, Hosoi K (2002) Divergent expression and localization of aquaporin 5, an exocrine-type water channel, in the submandibular gland of Sprague-Dawley rats. Pflugers Arch 445:405–412PubMedCrossRefGoogle Scholar
  139. Nakamoto T, Srivastava A, Romanenko VG, Ovitt CE, Perez-Cornejo P, Arreola J, Begenisich T, Melvin JE (2007) Functional and molecular characterization of the fluid secretion mechanism in human parotid acinar cells. Am J Physiol Regul Integr Comp Physiol 292:R2380–R2390PubMedGoogle Scholar
  140. Nakamoto T, Romanenko VG, Takahashi A, Begenisich T, Melvin JE (2008) Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibualr exocrine gland. Am J Physiol Cell Physiol 294:C810–C819PubMedCrossRefGoogle Scholar
  141. Nauntofte B, Poulsen JH (1986) Effects of Ca2+ and furosemide on Cl- transport and O2 uptake in rat parotid acini. Am J Physiol 251:C175–C185PubMedGoogle Scholar
  142. Nehrke K, Arreola J, Nguyen HV, Pilato J, Richardson L, Okunade G, Baggs R, Shull GE, Melvin JE (2002) Loss of hyperpolarization-activated Cl- current in salivary acinar cells from Clcn2 knockout mice. J Biol Chem 277:23604–23611PubMedCrossRefGoogle Scholar
  143. Nehrke K, Quinn CC, Begenisich T (2003) Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol 284:C535–C546PubMedGoogle Scholar
  144. Nguyen HV, Shull GE, Melvin JE (2000) Muscarinic receptor-induced acidification in sublingual mucous acinar cells: loss of pH recovery in Na+/H+ exchanger-1 deficient mice. J Physiol (Lond) 523:139–146CrossRefGoogle Scholar
  145. Nguyen HV, Stuart-Tilley A, Alper SL, Melvin JE (2004) Cl-/HCO3- exchange is acetazolamide sensitive and activated by a muscarinic receptor-induced [Ca2+]i increase in salivary acinar cells. Am J Physiol Gastrointest Liver Physiol 286:G312–G320PubMedCrossRefGoogle Scholar
  146. Nielsen S, King LS, Christensen BM, Agre P (1997) Aquaporins in complex tissues. II. Subcellular distribution in respiratory and glandular tissues of rat. Am J Physiol 273:C1549–C1561PubMedGoogle Scholar
  147. Novak I, Young JA (1986) Two independent ion transport systems in rabbit mandibular salivary glands. Pflugers Arch 407:649–656PubMedCrossRefGoogle Scholar
  148. Numata M, Petrecca K, Lake N, Orlowski J (1998) Identification of a mitochondrial Na+/H+ exchanger. J Biol Chem 273:6951–6959PubMedCrossRefGoogle Scholar
  149. Odgaard E, Jakobsen JK, Frische S, Praetorius J, Nielsen S, Aalkjaer C, Leipziger J (2004) Basolateral Na+-dependent HCO3- transporter NBCn1-mediated HCO3- influx in rat medullary thick ascending limb. J Physiol (Lond) 555:205–218CrossRefGoogle Scholar
  150. Oehlke O, Sprysch P, Rickmann M, Roussa E (2006) Na+/H+ exchanger isoforms are differentially regulated in rat submandibular gland during acid-base disturbances in vivo. Cell Tissue Res 323:253–262PubMedCrossRefGoogle Scholar
  151. Oehlke O, Martin HW, Osterberg N, Roussa E (2010) Rab11b and its effector Rip11 regulate the acidosis-induced traffic of V-ATPase in salivary ducts. J Cell Physiol. doi: 10.1002/jcp.22388 Google Scholar
  152. Ogawa Y, Fernley RT, Ito R, Ijuhin N (1998) Immunhistochemistry of carbonic anhydrase isoenzymes VI and II during development of the rat salivary glands. Histochem Cell Biol 110:81–88PubMedCrossRefGoogle Scholar
  153. Okada S, Misaka T, Tanaka Y, Matsumoto I, Ishibashi K, Sasaki S, Abe K (2008) Aquaporin-11 knockout mice and polycystic kidney disease animals share a common mechanism of cyst formation. FASEB J 22:3672–3684PubMedCrossRefGoogle Scholar
  154. Orlowski J, Kandasamy RA, Schull GE (1992) Molecular cloning and putative members of the Na+/H+ exchange gene family. J Biol Chem 267:9331–9339PubMedGoogle Scholar
  155. Park K, Olschowka JA, Richardson LA, Bookstein C, Chang EB, Melvin JE (1999) Expression of multiple Na+/H+ exchanger isoforms in rat parotid acinar and ductal cells. Am J Physiol 276:G470–G478PubMedGoogle Scholar
  156. Park K, Case RM, Brown PD (2001a) Identification and regulation of K+ and Cl- channels in human parotid acinar cells. Arch Oral Biol 46:801–810PubMedCrossRefGoogle Scholar
  157. Park K, Evans RL, Watson GE, Nehrke K, Richardson L, Bell SM, Schultheis PJ, Hand AR, Shull GE, Melvin JE (2001b) Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice. J Biol Chem 276:27042–27050PubMedCrossRefGoogle Scholar
  158. Park K, Hurley PT, Roussa E, Cooper GJ, Smith CP, Thévenod F, Steward MC, Case RM (2002) Expression of a sodium bicarbonate cotransporter in human parotid salivary glands. Arch Oral Biol 47:1–9PubMedCrossRefGoogle Scholar
  159. Passow H (1986) Molecular aspects of band 3 protein-mediated anion transport across the red blood cell membrane. Rev Physiol Biochem Pharmacol 103:61–203PubMedGoogle Scholar
  160. Pastor-Soler N, Beaulieu V, Litvin TN, Da Silva N, Chen Y, Brown D, Buck J, Levin LR, Breton S (2003) Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J Biol Chem 278:49523–49529PubMedCrossRefGoogle Scholar
  161. Pastor-Soler NM, Hallows KR, Smolak C, Gong F, Brown D, Breton S (2008) Alkaline pH- and cAMP-induced V-ATPase membrane accumulation is mediated by protein kinase A in epididymal clear cells. Am J Physiol Cell Physiol 294:C488–C494PubMedCrossRefGoogle Scholar
  162. Paulais M, Cragoe EJ Jr, Turner RJ (1994) Ion transport in rat parotid intralobular striated ducts. Am J Physiol 266:C1594–C1602PubMedGoogle Scholar
  163. Păunescu TG, Ljubojevic M, Russo LM, Winter C, McLaughlin MM, Wagner CA, Breton S, Brown D (2010) cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells. Am J Physiol Renal Physiol 298:F643–F654PubMedCrossRefGoogle Scholar
  164. Payne JA, Stevenson TJ, Donaldson LF (1996) Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform. J Biol Chem 271:16245–16252PubMedCrossRefGoogle Scholar
  165. Pearson MM, Lu J, Mount DB, Delpire E (2001) Localization of the K+-Cl- cotransporter, KCC3, in the central and peripheral nervous systems: expression in the choroid plexus, large neurons and white matter tracts. Neuroscience 103:481–491PubMedCrossRefGoogle Scholar
  166. Perry C, Baker OJ, Reyland ME, Grichtchenko II (2009) PKCα, β, γ, and PKCδ-dependent endocytosis of NBCe1-A and NBCe1-B in salivary parotid acinar cells. Am J Physiol Cell Physiol 297:C1409–C1423PubMedCrossRefGoogle Scholar
  167. Petersen OH (1986) Calcium-activated potassium channels and fluid secretion by exocrine glands. Am J Physiol 251:G1–G13PubMedGoogle Scholar
  168. Petersen OH, Poulsen JH (1967) Inhibition of salivary secretion and secretory potentials by g-strophantin, dinitrophenol and cyanide. Acta Physiol Scand 71:194–202PubMedCrossRefGoogle Scholar
  169. Pflüger EFW (1866) Ueber die Epithelian der Glandula submandibularis. Zbl Med Wiss 4:193-195Google Scholar
  170. Pirani D, Evans LA, Cook DI, Young JA (1987) Intracellular pH in the rat mandibular salivary gland: the role of Na-H and Cl-HCO3 antiports in secretion. Pflugers Arch 408:178–184PubMedCrossRefGoogle Scholar
  171. Planells-Cases R, Jentsch TJ (2009) Chloride channelopathies. Biochim Biophys Acta 1792:173–189PubMedGoogle Scholar
  172. Poronnik P, Schumann SY, Cook DI (1995) HCO3 -dependent ACh-activated Na + influx in sheep parotid secretory end pieces. Pflugers Arch 429:852–858PubMedCrossRefGoogle Scholar
  173. Race JE, Makhlouf FN, Logue PJ, Wilson FH, Dunham PB, Holtzman EJ (1999) Molecular cloning and functional characterizartion of KCC3, a new K-Cl cotransporter. Am J Physiol 277:C1210–C1219PubMedGoogle Scholar
  174. Rajendran VM, Black J, Ardito TA, Sangan P, Alper SL, Schweinfest C, Kashgarian M, Binder HJ (2000) Regulation of DRA and AE1 in rat colon by dietary Na depletion. Am J Physiol 279:G931–G942Google Scholar
  175. Reddy MM, Quinton PM (2003) Functional interaction of CFTR and ENaC in sweat glands. Pflugers Arch 445:499–503PubMedGoogle Scholar
  176. Reddy MM, Light MJ, Quinton PM (1999) Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function. Nature 402:301–304PubMedCrossRefGoogle Scholar
  177. Riordan JR (2005) Assembly of functional CFTR chloride channels. Annu Rev Physiol 67:701–718PubMedCrossRefGoogle Scholar
  178. Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, Pirvola U, Saarma M, Kaila K (1999) The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397:251–255PubMedCrossRefGoogle Scholar
  179. Robertson MA, Woodside M, Foskett JK, Orlowski J, Grinstein S (1997) Muscarinic agonists induce phosphorylation-independent activation of the NHE-1 isoform of the Na+/H+ antiporter in salivary acinar cells. J Biol Chem 272:287–294PubMedCrossRefGoogle Scholar
  180. Romanenko V, Nakamoto T, Srivastava A, Melvin JE, Begenisich T (2006) Molecular identification and physiological roles of parotid acinar cell maxi-K channels. J Biol Chem 281:27964–27972PubMedCrossRefGoogle Scholar
  181. Romanenko VG, Nakamoto T, Srivastava A, Begenisich T, Melvin JE (2007) Regulation of membrane potential and fluid secretion by Ca2+-activated K+ channels in mouse submandibular glands. J Physiol (Lond) 581:801–817CrossRefGoogle Scholar
  182. Romanenko VG, Nakamoto T, Catalán MA, Gonzalez-Begne M, Schwartz GJ, Jaramillo Y, Sepúlveda FV, Figueroa CD, Melvin JE (2008) Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands. Am J Physiol Gastrointest Liver Physiol 295:G1058–G1067PubMedCrossRefGoogle Scholar
  183. Romanenko VG, Catalán MA, Brown DA, Putzier I, Hartzell HC, Marmorstein AD, Gonzalez-Begne M, Rock JR, Harfe BD, Melvin JE (2010) Tmem16A encodes the Ca2+-activated Cl- channel in mouse submandibular salivary gland acinar cells. J Biol Chem 285:12990–13001PubMedCrossRefGoogle Scholar
  184. Romero MF, Hediger MA, Boulpaep EL, Boron WF (1997) Expression cloning and characterization of a renal electrogenic Na+-HCO3- cotransporter. Nature 387:409–413PubMedCrossRefGoogle Scholar
  185. Rossmann H, Sonnentag T, Heinzmann A, Seidler B, Bachmann O, Vieillard-Baron D, Gregor M, Seidler U (2001a) Differential expression and regulation of Na(+)/H(+) exchanger isoforms in rabbit parietal and mucous cells. Am J Physiol Gastrointest Liver Physiol 281:G447–G458PubMedGoogle Scholar
  186. Rossmann H, Bachmann O, Wang Z, Shull GE, Obermaier B, Stuart-Tilley A, Alper SL, Seidler U (2001b) Differential expression and regulation of AE2 anion exchanger subtypes in rabbit parietal and mucous cells. J Physiol (Lond) 534:837–848CrossRefGoogle Scholar
  187. Roussa E (2001) H+ and HCO3- transporters in human salivary ducts. An immunohistochemical study. Histochem J 33:337–344PubMedCrossRefGoogle Scholar
  188. Roussa E, Thévenod F (1998) Distribution of V-ATPase in rat salivary glands. Eur J Morphol 36 (Suppl):147–152PubMedGoogle Scholar
  189. Roussa E, Thévenod F, Sabolic I, Herak-Kramberger CM, Nastainczyk W, Bock R, Schulz I (1998) Immunolocalization of vacuolar type H+-ATPase in rat submandibular gland and adaptive changes induced by acid-base disturbances. J Histochem Cytochem 46:91–100PubMedGoogle Scholar
  190. Roussa E, Romero MF, Schmitt BM, Boron WF, Alper SL, Thévenod F (1999) Immunolocalization of anion exchanger AE2 and Na+-HCO3- cotransporter in rat parotid and submandibular glands. Am J Physiol Gastrointest Liver Physiol 40:G1288–G1296Google Scholar
  191. Roussa E, Alper SL, Thévenod F (2001) Immunolocalization of anion exchanger AE2, Na+/H+ exchangers NHE1 and NHE4, and vacuolar type H+-ATPase in rat pancreas. J Histochem Cytochem 49:463–474PubMedGoogle Scholar
  192. Roussa E, Shmukler BE, Wilhelm S, Casula S, Stuart-Tilley AK, Thévenod F, Alper SL (2002) Immunolocalization of potassium-chloride cotransporter polypeptides in rat exocrine glands. Histochem Cell Biol 117:335–344PubMedCrossRefGoogle Scholar
  193. Roussa E, Nastainszyk W, Thévenod F (2004) Differential expression of electrogenic NBC1 (SLC4A4) variants in rat kidney and pancreas. Biochem Biophys Res Commun 314:382–389PubMedCrossRefGoogle Scholar
  194. Roussa E, Wittschen P, Wolff NA, Torchalski B, Gruber AD, Thévenod F (2010) Cellular distribution and subcellular localization of mCLCA1/2 in murine gastrointestinal epithelia. J Histochem Cytochem 58:653–668PubMedCrossRefGoogle Scholar
  195. Sabolic I, Brown D, Gluck S, Alper SL (1997) Regulation of AE1 anion exchanger and H+-ATPase in rat cortex by acute metabolic acidosis and alkalosis. Kidney Int 51:125–137PubMedCrossRefGoogle Scholar
  196. Sardet C, Franchi A, Pouyssegur J (1989) Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter. Cell 56:271–280PubMedCrossRefGoogle Scholar
  197. Sato A, Miyoshi S (1988) Ultrastucture of the main excretory duct epithelia of the rat parotid and submandibular glands with review of the literature. Anat Rec 220:239–251PubMedCrossRefGoogle Scholar
  198. Sato A, Miyoshi S (1996) Tuft cells in the main excretory duct epithelia of the three major salivary glands. Eur J Morphol 34:225–228PubMedCrossRefGoogle Scholar
  199. Satoh H, Moriyama N, Hara C, Yamada H, Horita S, Kunimi M, Tsukamoto K, Iso-O N, Inatomi J, Kawakami H, Kudo A, Endou H, Igarashi T, Goto A, Fujita T, Seki G (2003) Localization of Na+-HCO3- cotransporter (NBC-1) variants in rat and human pancreas. Am J Physiol Cell Physiol 284:C729–C737PubMedGoogle Scholar
  200. Schlögel E, Young JA (1965) Micropuncture and perfusion investigation of sodium and potassium transport in the rat submaxillary gland. J Physiol (Lond) 183:73–75Google Scholar
  201. Schmitt BM, Biemesderfer D, Romero MF, Boulpaep EL, Boron WF (1999) NBC1 localization in the kidney. Immunolocalization of the electrogenic Na+HCO3- cotransporter in mammalian and amphibian kidney. Am J Physiol Renal Physiol 276:F27–F38Google Scholar
  202. Schneyer LH (1968) Secretory processes in perfused excretory duct of rat submaxillary gland. Am J Physiol 215:664–670PubMedGoogle Scholar
  203. Schneyer LH (1969) Secretion of potassium by perfused excretory duct of rat submaxillary gland. Am J Physiol 217:1324–1329PubMedGoogle Scholar
  204. Schneyer LH (1970) Amiloride inhibition of ion transport in perfused excretory duct of rat submaxillary gland. Am J Physiol 219:1050–1055PubMedGoogle Scholar
  205. Schneyer LH (1974) Effects of calcium on Na, K transport by perfused main duct of rat submaxillary gland. Am J Physiol 226:821–826PubMedGoogle Scholar
  206. Sciortino CM, Shrode LD, Fletcher BR, Harte PJ, Romero MF (2001) Localization of endogenous and recombinant Na+-driven anion exchanger protein NDAE1 from Drosophila melanogaster. Am J Physiol Cell Physiol 281:C449–C463PubMedGoogle Scholar
  207. Shackleford JM, Schneyer LH (1971) Ultrastructural aspects of the main excretory duct of rat submandibular gland. Anat Rec 169:679–696PubMedCrossRefGoogle Scholar
  208. Shcheynikov N, Yang D, Wang Y, Zeng W, Karniski LP, So I, Wall SM, Muallem S (2008) The Slc26a4 transporter functions as an electroneutral Cl-/I-/HCO3- exchanger: role of Slc26a4 and Slc26a6 in I- and HCO3- secretion and in regulation of CFTR in the parotid duct. J Physiol (Lond) 586:3813–3824CrossRefGoogle Scholar
  209. Sommer HM, Kaiser D, Drack E (1975) pH and bicarbonate excretion in the rat parotid gland as a function of salivary rate. Pflugers Arch 355:353–360PubMedCrossRefGoogle Scholar
  210. Spitzweg C, Joba W, Eisenmenger W, Heufelder AE (1998) Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 83:1746–1751PubMedCrossRefGoogle Scholar
  211. Srivastava A, Romanenko VG, Gonzalez-Begne M, Catalán MA, Melvin JE (2008) A variant of the Ca2+-activated Cl- channel Best3 is expressed in mouse exocrine glands. J Membr Biol 222:43–54PubMedCrossRefGoogle Scholar
  212. Steck TL (1974) The organization of proteins in the human red blood cell membrane. A review. J Cell Biol 62:1–19PubMedCrossRefGoogle Scholar
  213. Steinfeld S, Cogan E, King LS, Agre P, Kiss R, Delporte C (2001) Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren's syndrome patients. Lab Invest 81:143–148PubMedGoogle Scholar
  214. Sterling D, Reithmeier RAF, Casey JR (2001) A transport metabolon. Functional interaction of carbonic anhydrase II and chloride/bicarbonate exchangers. J Biol Chem 276:47886–47894PubMedGoogle Scholar
  215. Steward MC, Poronnik P, Cook DI (1996) Bicarbonate transport in sheep parotid secretory cells. J Physiol (Lond) 494:819–830Google Scholar
  216. Stuart-Tilley AK, Sardet C, Poyssegur J, Schwartz MA, Brown D, Alper SL (1994) Immunolocalization of anion exchanger AE2 and cation exchanger NHE-1 in distinct adjacent cells of gastric mucosa. Am J Physiol 266:C559–C568PubMedGoogle Scholar
  217. Stuart-Tilley AK, Shmukler BE, Brown D, Alper SL (1998) Immunolocalization and tissue specific splicing of AE2 anion exchanger in mouse kidney. J Am Soc Nephrol 9:946–959PubMedGoogle Scholar
  218. Su W, Shmuckler BE, Chernova MN, Stuart-Tilley AK, De Franceschi L, Brugnara C, Alper SL (1999) Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation. Am J Physiol 277:C899–C912PubMedGoogle Scholar
  219. Sugita M, Hirono C, Tanaka S, Nakahari T, Imai Y, Kanno Y, Shiba Y (2000) Visualization of the secretory process involved in Ca2+-activated fluid secretion from rat submandibular glands using the fluorescein dye, calcein. Eur J Cell Biol 79:182–191PubMedCrossRefGoogle Scholar
  220. Sun QF, Sun QH, Du J, Wang S (2008) Differential gene expression profiles of normal human parotid and submandibular glands. Oral Dis 14:500–509PubMedCrossRefGoogle Scholar
  221. Takahata T, Hayashi M, Ishikawa T (2002) SK4/IK1-like channels mediate tetraethylammonium insensitive, Ca2+-activated K+ currents in bovine parotid acinar cells. Am J Physiol Cell Physiol 284:C127–C144PubMedGoogle Scholar
  222. Tamarin AL, Sreebny M (1965) The rat submaxillary salivary gland. A correlative study by light and electron microscopy. J Morphol 117:295–352PubMedCrossRefGoogle Scholar
  223. Thaysen JH, Thorn NA, Schwartz IL (1954) Excretion of sodium, potassium, chloride and carbon dioxide in human parotid saliva. Am J Physiol 178:155–159PubMedGoogle Scholar
  224. Thévenod F (2002) Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 283:C651–C672PubMedGoogle Scholar
  225. Thomas E, Hay EM, Hajeer A, Silman AJ (1998) Sjögren’s syndrome: a community-based study of prevalence and impact. Br J Rheumatol 37:1069–1076PubMedCrossRefGoogle Scholar
  226. Thompson-Vest N, Shimizu Y, Hunne B, Furness JB (2006) The distribution of intermediate-conductance, calcium-activated, potassium (IK) channels in epithelial cells. J Anat 208:219–229PubMedCrossRefGoogle Scholar
  227. Tizzano EF, Chitayat D, Buchwald M (1993) Cell-specific localization of CFTR mRNA shows developmentally regulated expression in human fetal tissues. Hum Mol Genet 2:219–224PubMedCrossRefGoogle Scholar
  228. Trezise AE, Buchwald M (1991) In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator. Nature 353:434–437PubMedCrossRefGoogle Scholar
  229. Tse CM, Levine SA, Yun CH, Montrose MH, Little PJ, Pouyssegur J, Donowitz M (1993) Cloning and expression of a rabbit cDNA encoding a serum-activated ethylisopropylamiloride-resistant Na+/H+ exchanger isoform (NHE-2). J Biol Chem 268:11917–11924PubMedGoogle Scholar
  230. Tsubota K, Hirai S, King LS, Agre P, Ishida N (2001) Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren syndrome. Lancet 357:688–689PubMedCrossRefGoogle Scholar
  231. Tsuganezawa H, Kobayashi K, Iyori M, Araki T, Koizumi A, Watanabe S, Kaneko A, Fukao T, Monkawa T, Yoshida T, et al (2001) A new member of the HCO3- transporter superfamily is an apical anion exchanger of beta-intercalated cells in the kidney. J Biol Chem 276:8180–8189PubMedCrossRefGoogle Scholar
  232. Turner RJ, George JN (1988) Cl-/HCO3- exchange is present with Na+-K+Cl- cotransport in rabbit parotid acinar basolateral membranes. Am J Physiol 254:C391–C396PubMedGoogle Scholar
  233. Turner RJ, George JN, Baum BJ (1986) Evidence for a Na+/K+/Cl- cotransport system in basolateral vesicles from the rabbit parotid. J Membr Biol 94:143–152PubMedCrossRefGoogle Scholar
  234. Verkman AS, Yang B, Song Y, Manley GT, Ma T (2000) Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice. Exp Physiol 85:233S-241SPubMedCrossRefGoogle Scholar
  235. Walker JL, Menko AS, Khalil S, Rebustini I, Hoffman MP, Kreidberg JA, Kukuruzinska MA (2008) Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures. Dev Dyn 237:3128–3141PubMedCrossRefGoogle Scholar
  236. Wellner RB, Redman RS, Swaim WD, Baum BJ (2006) Further evidence for AQP8 expression in the myoepithelium of rat submandibular gland acinar cells. Pflugers Arch 441:49–56PubMedCrossRefGoogle Scholar
  237. Winston DC, Hennigar RA, Spicer SS, Garrett JR, Schulte BA (1988) Immunhistochemical localization of Na+, K+-ATPase in rodent and human salivary glands. J Histochem Cytochem 36:1139–1145PubMedGoogle Scholar
  238. Wu M-S, Biemesderfer D, Giebisch G, Aronson PS (1996) Role of NHE3 in mediating renal brush border Na+/H+ exchange. Adaptation to metabolic acidosis. J Biol Chem 271:32749–32752PubMedCrossRefGoogle Scholar
  239. Xu X, Zhao H, Diaz J, Muallem S (1995) Regulation of [Na+]i in resting and stimulated submandibular salivary ducts. J Biol Chem 270:19606–19612PubMedCrossRefGoogle Scholar
  240. Yamaguchi S, Ishikawa T (2005) Electrophysiological characterization of native Na+-HCO3- cotransporter current in bovine parotid acinar cells. J Physiol (Lond) 568:181–197CrossRefGoogle Scholar
  241. Yamazaki J, Okamura K, Ishibashi K, Kitamura K (2005) Characterization of CLCA protein expressed in ductal cells of rat salivary glands. Biochim Biophys Acta 1715:132–144PubMedCrossRefGoogle Scholar
  242. Yang B, Song Y, Zhao D, Verkman AS (2005a) Phenotype analysis of aquaporin-8 deficient mice. Am J Physiol 288:C1161–C1170CrossRefGoogle Scholar
  243. Yang B, Song Y, Zhao D, Verkman AS (2005b) Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell Physiol 288:C1161–C1170PubMedCrossRefGoogle Scholar
  244. Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U (2008) TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 455:1210–1215PubMedCrossRefGoogle Scholar
  245. Young JA (1968) Microperfusion investigation of chloride fluxes across the epithelium of the main excretory duct of the rat submaxillary gland. Pflugers Arch 303:366–374PubMedCrossRefGoogle Scholar
  246. Young JA, Van Lennep EW (1978) The morphology of salivary glands. Academic Press, LondonGoogle Scholar
  247. Young JA, Frömter E, Schögel E, Hamann KF (1967) A microperfusion investigation of sodium resorption and potassium secretion by the main excretory duct of the rat submaxillary gland. Pflugers Arch 295:157–172CrossRefGoogle Scholar
  248. Young JA, Martin CJ, Asz M, Weber FD (1970) A microperfusion investigation of bicarbonate secretion by the rat submaxillary gland. The action of a parasympathomimetic drug on electrolyte transport. Pflugers Arch 319:185–199PubMedCrossRefGoogle Scholar
  249. Young JA, Cook DI, Evans LAR, Pirani D (1987) Effects of ion transport inhibition on rat mandibular gland secretion. J Dent Res 66:531–535PubMedCrossRefGoogle Scholar
  250. Zeng W, Lee MG, Muallem S (1997) Membrane-specific regulation of Cl- channels by purinergic receptors in rat submandibular gland acinar and duct cells. J Biol Chem 272:32956–32965PubMedCrossRefGoogle Scholar
  251. Zhang GH, Melvin JE (1993) Membrane potential regulates Ca2+ uptake and inositol phosphate generation in rat sublingual mucous acini. Cell Calcium 14:551–562PubMedCrossRefGoogle Scholar
  252. Zhang GH, Cragoe EJ, Melvin JE (1992) Regulation of cytoplasmic pH in rat sublingual mucous acini at rest and during muscarinic stimulation. J Membr Biol 129:311–321PubMedGoogle Scholar
  253. Zhang GH, Cragoe EJ, Melvin JE (1993) Na+ influx is mediated by Na+-K+-2Cl- cotransport and Na+-H+ exchange in sublingual mucous acini. Am J Physiol 264:C54–C62PubMedGoogle Scholar
  254. Zhao H, Xu X, Diaz J, Muallem S (1995) Na+, K+, and H+/ HCO3- transport in submandibular salivary ducts. J Biol Chem 270:19599–19605PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Anatomy and Cell Biology II, Department of Molecular EmbryologyAlbert Ludwigs University FreiburgFreiburg i. Br.Germany

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