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Presence and Role of PACAP in Endocrine Glands of Mammals

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Pituitary Adenylate Cyclase Activating Polypeptide — PACAP

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 11))

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Abstract

PACAP is expressed and secreted by pituitary gonadotropes and folliculostellate cells, adrenal chromaffin cells, α- and β-cells of the Langerhans-islets, and some enteroendocrine cells. Low levels of PACAP produced by the abovementioned cells imply autocrine and paracrine actions. PACAP is also released into the portal circulation from some hypophysiotropic neurons and regulates pituitary functions. Because PACAP level is very low in the systemic circulation, other endocrine organs may not be under the influence of hypothalamic PACAP; however, they are innervated by PACAP immunoreactive sensory and the parasympathetic fibers. This means that PACAP is a neuromodulator in both the sensory and autonomic nervous systems of endocrine organs. The effect of PACAP is mediated through its specific receptors. The proliferating and differentiating effects of PACAP on endocrine tissues have also been demonstrated.

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References

  1. Dow RC, Bennie J, Fink G. Pituitary adenylate cyclase-activating peptide-38 (PACAP)-38 is released into hypophysial portal blood in the normal male and female rat. J Endocrinol. 1994;142:R1–4.

    Article  CAS  PubMed  Google Scholar 

  2. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, et al. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun. 1989;184:567–74.

    Article  Google Scholar 

  3. Arimura A, Somogyvári-Vigh A, Miyata A, Mizuno K, Coy DH, Kitada C. Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. Endocrinology. 1991;129:2787–9.

    Article  CAS  PubMed  Google Scholar 

  4. Köves K, Kántor O, Lakatos A, Szabó E, Kirilly E, Heinzlmann A, et al. Advent and recent advances in research on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of gonadotropic hormone secretion of female rats. J Mol Neurosci. 2014;54:494–511.

    Article  PubMed  CAS  Google Scholar 

  5. Ghatei MA, Takahashi K, Suzuki Y, Gardiner J, Jones PM, Bloom SR. Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissues. J Endocrinol. 1993;136:159–66.

    Article  CAS  PubMed  Google Scholar 

  6. Oka H, Jin L, Reubi JC, Qian X, Scheithauer BW, Fujii K, et al. Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas. Am J Pathol. 1998;153:1787–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Radleff-Schlimme A, Leonhardt S, Wuttke W, Jarry H. Evidence for PACAP to be an autocrine factor on gonadotrope cells. Ann NY Acad Sci. 1998;865:486–91.

    Article  CAS  PubMed  Google Scholar 

  8. Köves K, Kántor O, Scammel JG, Arimura A. PACAP colocalizes with luteinizing and follicle-stimulating hormone immunoreactivities in the anterior lobe of the pituitary gland. Peptides. 1998;19:1069–72.

    Article  PubMed  Google Scholar 

  9. Heinzlmann A, Kirilly E, Meltzer K, Szabó E, Baba A, Hashimoto H, et al. PACAP is transiently expressed in anterior pituitary gland of rats. In situ hybridization and cell immunoblot assay studies. Peptides. 2008;29:571–7.

    Article  CAS  PubMed  Google Scholar 

  10. Moore Jr JP, Burger LL, Dalkin AC, Winters SJ. Pituitary adenylate cyclase activating polypeptide messenger RNA in the paraventricular nucleus and anterior pituitary during the rat estrous cycle. Biol Reprod. 2005;73:491–9.

    Article  CAS  PubMed  Google Scholar 

  11. Winters SJ, Ghooray DT, Yang RQ, Holmes JB, O’Brien AR, Morgan J, et al. Dopamine-2 receptor activation suppresses PACAP expression in gonadotrophs. Endocrinology. 2014;155:2647–57.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Szabó E, Nemeskéri Á, Arimura A, Köves K. Effect of PACAP on LH release, studied by cell immunoblot assay, depends on the gender, on the time of day and in female rats on the day of estrous cycle. Regul Pept. 2004;123:139–45.

    Article  PubMed  CAS  Google Scholar 

  13. Szabó E, Nemeskéri A, Heinzlmann A, Suzuki N, Arimura A, Köves K. Cell immunoblot assay study demonstrating the release of PACAP from individual anterior pituitary cells of rats and the effect of PACAP on LH release. Regul Pept. 2002;109:75–81.

    Article  PubMed  Google Scholar 

  14. Jin L, Tsumanuma I, Ruebel KH, Bayliss JM, Lloyd RV. Analysis of homogenous population of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription polymerase chain reaction. Endocrinology. 2001;142:1703–9.

    CAS  PubMed  Google Scholar 

  15. Winters SJ, Moore Jr JP. PACAP, an autocrine/paracrine regulator of gonadotrophs. Biol Reprod. 2011;84:844–50.

    Article  CAS  PubMed  Google Scholar 

  16. Tsujii T, Winters SJ. Effects of pulsatile pituitary adenylate cyclase activating polypeptide (PACAP) on gonadotropin secretion and subunit mRNA levels in perifused rat pituitary cells. Life Sci. 1995;56:1103–11.

    Article  CAS  PubMed  Google Scholar 

  17. Tsujii T, Ishizaka K, Winters SJ. Effects of pituitary adenylate cyclase-activating polypeptide on gonadotropin secretion and subunit messenger ribonucleic acids in perifused rat pituitary cells. Endocrinology. 1994;135:826–33.

    CAS  PubMed  Google Scholar 

  18. Vigh S, Arimura A, Gottschall PE, Kitada C, Somogyvári-Vigh A, Childs GV. Cytochemical characterization of anterior pituitary target cells for the neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), using biotinylated ligands. Peptides. 1993;14:59–65.

    Article  CAS  PubMed  Google Scholar 

  19. Vertongen P, Velkeniers B, Hooghe-Peters E, Robberecht P. Differential alternative splicing of PACAP receptor in pituitary cell subpopulations. Mol Cell Endocrinol. 1995;113:131–5.

    Article  CAS  PubMed  Google Scholar 

  20. Coleman DT, Chen X, Sassaroli M, Bancroft C. Pituitary adenylate cyclase-activating polypeptide regulates prolactin promoter activity via a protein kinase A-mediated pathway that is independent of the transcriptional pathway employed by thyrotropin-releasing hormone. Endocrinology. 1996;137:1276–85.

    CAS  PubMed  Google Scholar 

  21. Bresson-Bepoldin L, Jacquot MC, Schlegel W, Rawlings SR. Multiple splice variants of the pituitary adenylate cyclase-activating polypeptide type 1 receptor detected by RT-PCR in single rat pituitary cells. J Mol Endocrinol. 1998;21:109–20.

    Article  CAS  PubMed  Google Scholar 

  22. Propato-Mussafiri R, Kanse SM, Ghatei MA, Bloom SR. Pituitary adenylate cyclase-activating polypeptide releases 7B2, adrenocorticotrophin, growth hormone and prolactin from the mouse and rat clonal pituitary cell lines AtT-20 and GH3. J Endocrinol. 1992;132:107–13.

    Article  CAS  PubMed  Google Scholar 

  23. Rawlings SR, Piuz I, Schlegel W, Bockaert J, Journot L. Differential expression of pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide receptor subtypes in clonal pituitary somatotrophs and gonadotrophs. Endocrinology. 1995;136:2088–98.

    CAS  PubMed  Google Scholar 

  24. Dejda A, Bourgault S, Doan ND, Létourneau M, Couvineau A, Vaudry H, et al. Identification by photoaffinity labeling of the extracellular N-terminal domain of PAC1 receptor as the major binding site for PACAP. Biochimie. 2011;93:669–77.

    Article  CAS  PubMed  Google Scholar 

  25. Jarry H, Leonhardt S, Schmidt WE, Creutzfeldt W, Wuttke W. Contrasting effects of pituitary adenylate cyclase activating polypeptide (PACAP) on in vivo and in vitro prolactin and growth hormone release in male rats. Life Sci. 1992;51:823–30.

    Article  CAS  PubMed  Google Scholar 

  26. Góth MI, Lyons CE, Canny BJ, Thorner MO. Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. Endocrinology. 1992;130:939–44.

    PubMed  Google Scholar 

  27. Velkeniers B, Zheng L, Kazemzadeh M, Robberecht P, Vanhaelst L, Hooghe-Peters EL. Effect of pituitary adenylate cyclase-activating polypeptide 38 on growth hormone and prolactin expression. J Endocrinol. 1994;143:1–11.

    Article  CAS  PubMed  Google Scholar 

  28. Yamauchi K, Murakami Y, Koshimura K, Nishiki M, Tanaka J, Kato Y. Involvement of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone secretion induced by serotoninergic mechanisms in the rat. Endocrinology. 1996;137:1693–7.

    CAS  PubMed  Google Scholar 

  29. Grafer CM, Thomas R, Lambrakos L, Montoya I, White S, Halvorson LM. GnRH stimulates expression of PACAP in the pituitary gonadotropes via both the PKA and PKC signaling systems. Mol Endocrinol. 2009;23:1022–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Larivière S, Garrel G, Robin MT, Counis R, Cohen-Tannoudji J. Differential mechanisms for PACAP and GnRH cAMP induction contribute to cross-talk between both hormones in the gonadotrope LbetaT2 cell line. Ann N Y Acad Sci. 2006;1070:376–9.

    Article  PubMed  CAS  Google Scholar 

  31. Culler MD, Paschall CS. Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates the gonadotropin-releasing activity of luteinizing hormone-releasing hormone. Endocrinology. 1991;129:2260–2.

    Article  CAS  PubMed  Google Scholar 

  32. Alarcón P, García-Sancho J. Differential calcium responses to the pituitary adenylate cyclase-activating polypeptide (PACAP) in the five main cell types of rat anterior pituitary. Pflugers Arch. 2000;440:685–91.

    Article  PubMed  Google Scholar 

  33. Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12:151–80.

    Article  CAS  PubMed  Google Scholar 

  34. Moore RY, Sibony P. Enkephalin-like immunoreactivity in neurons in the human pineal gland. Brain Res. 1988;457:395–8.

    Article  CAS  PubMed  Google Scholar 

  35. Matsushima S, Sakai Y, Hira Y, Oomori Y, Daikoku S. Immunohistochemical studies on sympathetic and non-sympathetic nerve fibers and neuronal cell bodies in the pineal gland of cotton rats. Sigmodon Hispidus Arch Histol Cytol. 1994;57:47–58.

    Article  CAS  PubMed  Google Scholar 

  36. Ichimura T, Arikuni T, Hashimoto PH. Fine-structural study of the pineal body of 3 monkey (Macaca fuscata) with special reference to synaptic formations. Cell Tissue Res. 1986;244:569–76.

    Article  CAS  PubMed  Google Scholar 

  37. Csáki Á, Vígh B, Boldogkői Z, Vereczki V, Szél Á, Köves K. Is a neuronal chain between the pineal body and the retina in rats and hamsters? Transneural tracing studies. Neurosci Lett. 2015;588:1–6.

    Article  PubMed  CAS  Google Scholar 

  38. Baeres FM, Møller M. Demonstration of PACAP-immunoreactive intrapineal nerve fibers in the golden hamster (Mesocricetus auratus) originating from the trigeminal ganglion. J Pineal Res. 2005;38:116–22.

    Article  CAS  PubMed  Google Scholar 

  39. Moller M, Baeres FM. The anatomy and innervation of the mammalian pineal gland. Cell Tissue Res. 2002;309:139–50.

    Article  CAS  PubMed  Google Scholar 

  40. Phansuwan-Pujito P, Møller M, Govitrapong P. Cholinergic innervation and function in the mammalian pineal gland. Microsc Res Tech. 1999;46:281–95.

    Article  CAS  PubMed  Google Scholar 

  41. Simonneaux V, Kienlen-Campard P, Loeffler JP, Basille M, Gonzalez BJ, Vaudry H, et al. Pharmacological, molecular and functional characterization of vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptors in the rat pineal gland. Neuroscience. 1998;85:887–96.

    Article  CAS  PubMed  Google Scholar 

  42. Simonneaux V, Ouichou A, Pévet P. Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates melatonin synthesis from rat pineal gland. Brain Res. 1993;603:148–52.

    Article  CAS  PubMed  Google Scholar 

  43. Yuwiler A, Brammer GL, Bennett BL. Interaction between adrenergic and peptide stimulation in the rat pineal: pituitary adenylate cyclase-activating peptide. J Neurochem. 1995;64:2273–80.

    Article  CAS  PubMed  Google Scholar 

  44. Ribelayga C, Pévet P, Simonneaux V. Adrenergic and peptidergic regulations of hydroxyindole-O-methyltransferase activity in rat pineal gland. Brain Res. 1997;777:247–50.

    Article  CAS  PubMed  Google Scholar 

  45. Chik CL, Liu QY, Li B, Klein DC, Zylka M, Kim DS, et al. Alpha 1D L-type Ca(2+)-channel currents: inhibition by a beta-adrenergic agonist and pituitary adenylate cyclase-activating polypeptide (PACAP) in rat pinealocytes. J Neurochem. 1997;68:1078–87.

    Article  CAS  PubMed  Google Scholar 

  46. Fahrenkrug J, Hannibal J. Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands. Gen Comp Endocrinol. 2011;171:105–13.

    Article  CAS  PubMed  Google Scholar 

  47. Chen W, Inui T, Hachiya T, Ochi Y, Nakajima Y, Kajita Y. Stimulatory action of pituitary adenylate cyclase-activating polypeptide (PACAP) on thyroid gland. Biochem Biophys Res Commun. 1993;194:923–9.

    Article  CAS  PubMed  Google Scholar 

  48. Watts AG, Sanchez-Watts G. Physiological regulation of peptide messenger RNA colocalization in rat hypothalamic paraventricular medial parvicellular neurons. J Comp Neurol. 1995;352:501–14.

    Article  CAS  PubMed  Google Scholar 

  49. Watts AG. Glucocorticoid regulation of peptide genes in neuroendocrine CRH neurons: a complexity beyond negative feedback. Front Neuroendocrinol. 2005;26:109–30.

    Article  CAS  PubMed  Google Scholar 

  50. Eiden LE. Neuropeptide–catecholamine interactions in stress. Adv Pharmacol. 2013;68:399–404.Tornøe K, Hannibal J, Jensen TB, Georg B, Rickelt LF, Andreasen MB, et al. PACAP-(1-38) as neurotransmitter in the porcine adrenal glands. Am J Physiol Endocrinol Metab. 2000;279:E1413–25.

    Google Scholar 

  51. Tornøe K, Hannibal J, Jensen TB, Georg B, Rickelt LF, Andreasen MB, et al. PACAP-(1-38) as neurotransmitter in the porcine adrenal glands. Am J Physiol Endocrinol Metab. 2000;279:E1413–25.

    PubMed  Google Scholar 

  52. Tabarin A, Chen D, Håkanson R, Sundler F. Pituitary adenylate cyclase-activating peptide in the adrenal gland of mammals: distribution, characterization and responses to drugs. Neuroendocrinology. 1994;59:113–9.

    Article  CAS  PubMed  Google Scholar 

  53. Kántor O, Heinzlmann A, Suzuki N, Vincze E, Kocsis K, Köves K. Distribution of PACAP and its mRNA in several nonneural tissues of rats demonstrated by sandwich enzyme immunoassay and RT-PCR technique. Regul Pept. 2002;109:103–5.

    Article  PubMed  Google Scholar 

  54. Conconi MT, Spinazzi R, Nussdorfer GG. Endogenous ligands of PACAP/VIP receptors in the autocrine–paracrine regulation of the adrenal gland. Int Rev Cytol. 2006;249:1–51.

    Article  CAS  PubMed  Google Scholar 

  55. Hannibal J. Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study. J Comp Neurol. 2002;453:389–417.

    Article  CAS  PubMed  Google Scholar 

  56. Hashimoto H, Nogi H, Mori K, Ohishi H, Shigemoto R, Yamamoto K, et al. Distribution of mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study. J Comp Neurol. 1996;371:567–77.

    Article  CAS  PubMed  Google Scholar 

  57. Stroth N, Holighaus Y, Ait-Ali D, Eiden LE. PACAP: a master regulator of neuroendocrine stress circuits and the cellular stress response. Ann N Y Acad Sci. 2011;1220:49–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hamelink C, Weihe E, Eiden LE. PACAP: an “emergency response” co-transmitter in the adrenal medulla. In: Vaudry H, Arimura A, editors. Pituitary adenylate cyclase-activating polypeptide. Norwell, MA: Kluwer-Academic Press; 2003. p. 227–50.

    Chapter  Google Scholar 

  59. Girard BM, May V, Bora SH, Fina F, Braas KM. Regulation of neurotrophic peptide expression in sympathetic neurons: quantitative analysis using radioimmunoassay and real-time quantitative polymerase chain reaction. Regul Pept. 2002;109:89–101.

    Article  CAS  PubMed  Google Scholar 

  60. Kvetnanský R, Pacák K, Fukuhara K, Viskupic E, Hiremagalur B, Nankova B, et al. Sympathoadrenal system in stress. Interaction with the hypothalamic-pituitary-adrenocortical system. Ann N Y Acad Sci. 1995;771:131–58.

    Article  PubMed  Google Scholar 

  61. Kvetnansky R, Sabban EL, Palkovits M. Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev. 2009;89:535–606.

    Article  CAS  PubMed  Google Scholar 

  62. Hammack SE, Cheung J, Rhodes KM, Schutz KC, Falls WA, Braas KM, et al. Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior. Psychoneuroendocrinology. 2009;34:833–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hammack SE, Roman CW, Lezak KR, Kocho-Shellenberg M, Grimmig B, Falls WA, et al. Roles for pituitary adenylate cyclase-activating peptide (PACAP) expression and signaling in the bed nucleus of the stria terminalis (BNST) in mediating the behavioral consequences of chronic stress. J Mol Neurosci. 2010;42:327–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tanguy Y, Falluel-Morel A, Arthaud S, Boukhzar L, Manecka DL, Chagraoui A, et al. The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes. Endocrinology. 2011;152:4322–35.

    Article  CAS  PubMed  Google Scholar 

  65. Woods SC, Porte Jr D. Neural control of the endocrine pancreas. Physiol Rev. 1974;54:596–619.

    CAS  PubMed  Google Scholar 

  66. Yi E, Smith TG, Love JA. Noradrenergic innervation of rabbit pancreatic ganglia. Auton Neurosci. 2005;117:87–96.

    Article  CAS  PubMed  Google Scholar 

  67. Sharkey KA, Williams RG, Dockray GJ. Sensory substance P innervation of the stomach and pancreas. Demonstration of capsaicin-sensitive sensory neurons in the rat by combined immunohistochemistry and retrograde tracing. Gastroenterology. 1984;87:914–21.

    CAS  PubMed  Google Scholar 

  68. Fridolf T, Sundler F, Ahren B. Pituitary adenylate cyclase-activating polypeptide (PACAP): occurrence in rodent pancreas and effects on insulin and glucagon secretion in the mouse. Cell Tissue Res. 1992;269:275–9.

    Article  CAS  PubMed  Google Scholar 

  69. Köves K, Arimura A, Vigh S, Somogyvári-Vigh A, Miller J. Immunohistochemical localization of PACAP in the ovine digestive system. Peptides. 1993;14:449–55.

    Article  PubMed  Google Scholar 

  70. Filipsson K, Sundler F, Hannibal J, Ahren B. PACAP and PACAP receptors in insulin producing tissues: localization and effects. Regul Pept. 1998;74:167–75.

    Article  CAS  PubMed  Google Scholar 

  71. Filipsson K, Kvist-Reimer M, Ahren B. The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet function. Diabetes. 2001;50:1959–69.

    Article  CAS  PubMed  Google Scholar 

  72. Yada T, Sakuradan M, Ihidall K, Nakata M, Muratall F, Arimura A, et al. Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet P-cells. J Biol Chem. 1994;269:1290–3.

    CAS  PubMed  Google Scholar 

  73. Portela-Gomes GM, Lukinius A, Ljungberg O, Efendic S, Ahrén B, Abdel-Halim SM. PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas. Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets. Regul Pept. 2003;113:31–9.

    Article  CAS  PubMed  Google Scholar 

  74. Inagaki N, Yoshida H, Mizuta M, Mizuno N, Fujii Y, Gonoi T, et al. Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells. Proc Natl Acad Sci U S A. 1994;91:2679–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Borboni P, Porzio O, Pierucci D, Cicconi S, Magnaterra R, Federici M, et al. Molecular and functional characterization of pituitary adenylate cyclase-activating polypeptide (PACAP-38)/vasoactive intestinal polypeptide receptors in pancreatic beta-cells and effects of PACAP-38 on components of the insulin secretory system. Endocrinology. 1999;140:5530–7.

    CAS  PubMed  Google Scholar 

  76. Yada T, Sakurada M, Nakata M, Yaekura K, Kikuchi M. PACAP as low as 10(-13) M raises cytosolic Ca2+ activity in pancreatic B-cells by augmenting Ca2+ influx through L-type Ca2+ channels to trigger insulin release. Adv Exp Med Biol. 1997;426:165–71.

    Article  CAS  PubMed  Google Scholar 

  77. Filipsson K, Tornoe K, Holst JJ, Ahrén B. Pituitary adenylate cyclase activating polypeptide stimulates insulin and glucagon secretion in humans. J Clin Endocrinol Metab. 1997;82:3093–8.

    CAS  PubMed  Google Scholar 

  78. Kawai K, Yokota C, Ohashi S, Isobe K, Suzuki S, Nakai T, et al. Pituitary adenylate cyclase-activating polypeptide: effects on pancreatic-adrenal hormone secretion and glucose-lipid metabolism in normal conscious dogs. Metabolism. 1994;43:739–44.

    Article  CAS  PubMed  Google Scholar 

  79. Seki Y, Suzuki Y, Baskaya MK, Kano T, Saito K, Takayasu M, et al. The effects of pituitary adenylate cyclase-activating polypeptide on cerebral arteries and vertebral artery blood flow in anesthetized dogs. Eur J Pharmacol. 1995;275:259–66.

    Article  CAS  PubMed  Google Scholar 

  80. Carlsson PO, Ostenson CG, Efendic S, Langel U, Jansson L. Pituitary adenylate cyclase activating polypeptide (PACAP) redistributes the blood within the pancreas of anesthetized rats. Regul Pept. 1996;63:123–8.Kulkarni RN, Smith DM, Ghatei MA, Bloom SR. A 67 kDa protein mediates pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide-stimulated insulin secretion in a hamster clonal beta-cell line. J Endocrinol. 1995;147:120-30.

    Google Scholar 

  81. Kulkarni RN, Smith DM, Ghatei MA, Bloom SR. A 67 kDa protein mediates pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide-stimulated insulin secretion in a hamster clonal beta-cell line. J Endocrinol. 1995;147:120–30.

    Article  Google Scholar 

  82. Tornøe K, Hannibal J, Fahrenkrug J, Holst JJ. PACAP-(1-38) as neurotransmitter in pig pancreas: receptor activation revealed by the antagonist PACAP-(6-38). Am J Physiol. 1997;273:G436–46.

    PubMed  Google Scholar 

  83. Nakata M, Shintani N, Hashimoto H, Baba A, Yada T. Intra-islet PACAP protects pancreatic β-cells against glucotoxicity and lipotoxicity. J Mol Neurosci. 2010;42:404–10.

    Article  CAS  PubMed  Google Scholar 

  84. Filipsson K, Sundler F, Ahrén B. PACAP is an islet neuropeptide which contributes to glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 1999;256:664–7.

    Article  CAS  PubMed  Google Scholar 

  85. Jamen F, Persson K, Bertrand G, Rodriguez-Henche N, Puech R, Bockaert J, et al. PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance. J Clin Invest. 2000;105:1307–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Persson K, Ahrén B. The neuropeptide PACAP contributes to the glucagon response to insulin-induced hypoglycaemia in mice. Acta Physiol Scand. 2002;175:25–8.

    Article  CAS  PubMed  Google Scholar 

  87. Asnicar MA, Köster A, Heiman ML, Tinsley F, Smith DP, Galbreath E, et al. Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide receptor 2 deficiency in mice results in growth retardation and increased basal metabolic rate. Endocrinology. 2002;143:3994–4006.

    Article  CAS  PubMed  Google Scholar 

  88. Fabricius D, Karacay B, Shutt D, Leverich W, Schafer B, Takle E, et al. Characterization of intestinal and pancreatic dysfunction in VPAC1-null mutant mouse. Pancreas. 2011;40:861–71.

    Article  CAS  PubMed  Google Scholar 

  89. Yamamoto K, Hashimoto H, Tomimoto S, Shintani N, Miyazaki J, Tashiro F, et al. Overexpression of PACAP in transgenic mouse pancreatic beta-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes. Diabetes. 2003;52:1155–62.

    Article  CAS  PubMed  Google Scholar 

  90. Han B, Wu J. DcR3 protects islet β cells from apoptosis through modulating Adcyap1 and Bank1 expression. J Immunol. 2009;183:8157–66.

    Article  CAS  PubMed  Google Scholar 

  91. Sanlioglu AD, Karacay B, Balci MK, Thomas S, Griffith TS, Sanlioglu S. Therapeutic potential of VIP vs PACAP in diabetes. J Mol Endocrinol. 2012;49:R157–67.

    Article  CAS  PubMed  Google Scholar 

  92. Sundler F, Ekblad E, Absood A, Håkanson R, Köves K, Arimura A. Pituitary adenylate cyclase activating peptide: a novel vasoactive intestinal peptide-like neuropeptide in the gut. Neuroscience. 1992;46:439–54.

    Article  CAS  PubMed  Google Scholar 

  93. Vincze E, Kántor O, Kausz M, Németh J, Arimura A, Gonda P, et al. Comparative study on the appearance of various bioactive peptides in foregut derivates during the ontogenesis. J Physiol Paris. 2001;95:99–103.

    Article  CAS  PubMed  Google Scholar 

  94. Vincze É, Kántor O, Kiss A, Gonda G, Gombás P, Kiss J, et al. Pituitary adenylate cyclase activating polypeptide (PACAP) is present in human and cat gastric glands. Peptides. 1999;20:937–41.

    Article  CAS  PubMed  Google Scholar 

  95. Smolka A, Donaldson Jr RM. Monoclonal antibodies to human intrinsic factor. Gastroenterology. 1990;98:607–14.

    Article  CAS  PubMed  Google Scholar 

  96. Oh DS, Lieu SN, Yamaguchi DJ, Tachiki K, Lambrecht N, Ohning GV, et al. PACAP regulation of secretion and proliferation of pure populations of gastric ECL cells. J Mol Neurosci. 2005;26:85–97.

    Article  CAS  PubMed  Google Scholar 

  97. Piqueras L, Taché Y, Martínez V. Peripheral PACAP inhibits gastric acid secretion through somatostatin release in mice. Br J Pharmacol. 2004;142:67–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Pisegna JR, Ohning GV, Athmann C, Zeng N, Walsh JH, Sachs G. Role of PACAP1 receptor in regulation of ECL cells and gastric acid secretion by pituitary adenylate cyclase activating peptide. Ann N Y Acad Sci. 2000;921:233–41.

    Article  CAS  PubMed  Google Scholar 

  99. Sandvik AK, Cui G, Bakke I, Munkvold B, Waldum HL. PACAP stimulates gastric acid secretion in the rat by inducing histamine release. Am J Physiol Gastrointest Liver Physiol. 2001;281:G997–1003.

    CAS  PubMed  Google Scholar 

  100. Holgert H, Holmberg K, Hannibal J, Fahrenkrug J, Brimijoin S, Hartman BK, et al. PACAP in the adrenal gland relationship with choline acetyltransferase, enkephalin and chromaffin cells and effects of immunological sympathectomy. Neuroreport. 1996;8:297–301.

    Article  CAS  PubMed  Google Scholar 

  101. Köves K, Molnár J, Kántor O, Lakatos A, Görcs T, Somogyvári-Vigh A, et al. PACAP participates in the regulation of the hormonal events preceeding the ovulation. Acta Biol Hung. 1996;47:239–49.

    PubMed  Google Scholar 

  102. Sawangjaroen K, Curlewis JD. Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) on prolactin, luteinizing hormone and growth hormone secretion in the ewe. J Neuroendocrinol. 1994;6:549–55.

    Article  CAS  PubMed  Google Scholar 

  103. Osuga Y, Mitsuhashi N, Mizuno M. In vivo effect of pituitary adenylate cyclase activating polypeptide 38 (PACAP 38) on the secretion of luteinizing hormone (LH) in male rats. Endocrinol Jpn. 1992;39:153–6.

    Article  CAS  PubMed  Google Scholar 

  104. Kawai K, Ohse C, Watanabe Y, Suzuki S, Yamashita K, Ohashi S. Pituitary adenylate cyclase activating polypeptide stimulates insulin release from the isolated perfused rat pancreas. Life Sci. 1992;50:257–61.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Katalin Koves .

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Koves, K. (2016). Presence and Role of PACAP in Endocrine Glands of Mammals. In: Reglodi, D., Tamas, A. (eds) Pituitary Adenylate Cyclase Activating Polypeptide — PACAP. Current Topics in Neurotoxicity, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-35135-3_11

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