Abstract
Peptide hormones control salt reabsorption in cortical thick ascending limb (cTAL) cells of the loop of Henle. These agonists act, in part, through alterations on intracellular Ca2+ ([Ca2+]i). Primary cell cultures were prepared from porcine kidneys using a double antibody technique (goat antihuman Tamm-Horsfall and rabbit antigoat IgG antibodies). [Ca2+]i was determined in single cells with fluorescent techniques using fura-2. Parathyroid hormone (PTH) and arginine vasopressin (AVP) transiently increased [Ca2+]i in a dose-dependent manner. [Ca2+]i maximally increased from 85±5 nmol/l to 608±99 nmol/l with PTH, 10−6M, and to 766±162 nmol/l with AVP, 10−7 M. The increment in [Ca2+]i by both hormones was by intracellular Ca2+ release and entry through plasma membrane Ca2+ channels. 8-Bromoadenosine-3′, 5′-cyclic monophosphate (8-BrcAMP), 10−4M, increased [Ca2+]i(basal 83±3 to 427±121 nmol/l) but only from internal sources as nifedipine (10 μmol), ([Ca2+]i changes: 86±4 to 390±29 nmol/l) and removal of bath Ca 2+o , ([Ca2+]ichanges: 84±6 to 517±142 nmol/l), were without effect on agonist-induced [Ca2+]i. Thapsigargin, 1.5 μmol, completely abolished the AVP- and cyclic adenosine monophosphate-(cAMP)-induced Ca2+ transients, and partially inhibited PTH-mediated Ca2+ transients by about 50%. Pretreatment with 8-BrcAMP inhibited the PTH and AVP responses likely through depletion of cAMP-sensitive Ca2+ stores. Activation of protein kinase C (PKC) with phorbol esters inhibited PTH and AVP responses and 8-BrcAMP-induced [Ca2+]i transients. The responses partially returned following down-regulation of PKC with prolonged exposure to phorbol esters. These data suggest that PKC activation modulates agonist-induced Ca2+ release and entry, possibly through actions on intracellular release mechanisms. In summary, PTH and AVP stimulate Ca2+ signals by similar pathways involving cAMP and inositol 1,3,4-trisphosphate activity at similar sites on the endoplasmic reticulum and plasma membrane. These results suggest that peptide hormones may act through Ca2+ and be modulated by different pathways which may have diverse effects on cTAL function.
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References
Ansah T-A, Dho S, Case RM (1986) Calcium concentration and amylase secretion in guinea pig pancreatic acini: interactions between carbachol, cholecystokinin, octapeptide, and the phorbol ester, 12-0-tetradecanoylphorbol 13-acetate. Biochim Biophys Acta 889:326–333
Bailly C, Roinel N, Amiel C (1984) PTH-like glucagon stimulation of Ca and Mg reabsorption in Henle's loop of the rat. Am J Physiol 246:F205-F212
Berridge MJ (1993) Inositol triphosphate and calcium signalling. Nature 361:315–325
Bird G St J, Rossier MF, Obie JF, Putney JW Jr (1993) Sinusoidal oscillations in intracellular calcium requiring negative feedback by protein kinase C. J Biol Chem 268:8425–8428
Bourdeau JE, Eby BK, Hu J (1990) cAMP-stimulated rise of [Ca2+]i in rabbit connecting tubules: role of peritubular calcium. Am J Physiol 258:F751-F755
Bruzzone R, Regazzi R, Wollheim C (1988) Caerulin causes translocation of protein kinase C in rat acini without increasing cytosolic free Ca2+. Am J Physiol 255:G33-G39
Chabardès D, Imbert M, Clique A, Montégut M, Morel F (1975) PTH sensitive adenyl cyclase activity in different segments of the rabbit nephron. Pflügers Arch 354:229–239
Dai L-j, Quamme GA (1991) Intracellular Mg2+ and magnesium depletion in isolated renal thick ascending limb cells. J Clin Invest 88:1255–1264
Di Stefano A, Wittner M, Nitschke R, Braitsch R, Greger R, Bailly C, Amiel C, Roinel N, de Rouffignac C (1990) Effects of parathyroid hormone and calcitonin on Na+, Cl−, K+, Mg2+ and Ca2+ transport in cortical and medullary thick ascending limbs of mouse kidney. Pflügers Arch 417:161–167
Dublineau I, Elalouf J-M, Pradelles P, de Rouffignac C (1989) Independent desensitization of rat renal thick ascending limbs and collecting ducts to ADH. Am J Physiol 256:F656-F663
Elalouf JM, Chabanne-Sari S, de Rouffignac C (1986) Additivity of the effects of glucagon and vasopressin on renal Mg reabsorption and urinary concentration ability in the rat. Pflügers Arch 407:566–571
Elalouf JM, Di Stefano A, de Rouffignac C (1986) Sensitivities of rat kidney thick ascending limbs and collecting ducts to vasopressin (in vivo). Proc Natl Acad Sci USA 83:2276–2280
Elalouf JM, Chabane-Sari S, Roinel N, de Rouffignac C (1988) Desensitization of rat renal thick ascending limb to vasopressin. Proc Nat Acad Sci USA 85:2407–2416
Glennon MC, Bird GSJ, Kwan C-y, Putney J Jr (1992) Actions of vasopressin and the Ca2+-ATPase inhibitor, thapsigargin, on Ca2+ signalling in hepatocytes. J Biol Chem 267:8230–8233
Greger R (1985) Ion transport mechanisms in thick ascending limb of Henle's loop of mammalian nephron. Physiol Rev 65:760–797
Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indications with greatly improved fluorescence properties. J Biol Chem 260:3440–3450
Hallam TJ, Rink TJ (1989) Receptor-mediated Ca2+ entry in diversity of function and mechanism. Trends Pharmacol Sci 10:8–10
Herbert SC, Andreoli TE (1984) Control of NaCl transport in the thick ascending limb. Am J Physiol 246:F745-F756
Horn VJ, Baum BJ, Ambudkar IS (1988)β-Adrenergic receptor stimulation induces inositol trisphosphate production and Ca2+ mobilization in rat acinar cells. J Biol Chem 263: 12454–12460
Kikkawa U, Nishizuka Y (1986) The role of protein kinase C in transmembrane signalling. Annu Rev Cell Biol 2:149–178
Kuno M, Gardner P (1987) Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes. Nature 326:301–304
Luini A, Lewis D, Guild S, Corda D, Axelrod J (1985) Hormone secretagogues increase cytosolic calcium by increasing cAMP in corticotropin-secreting cells. Proc Natl Acad Sci USA 82:8034–8038
Mauger J-P, Claret M (1986) Mobilization of intracellular calcium by glucagon and cyclic AMP analogues in isolated rat hepatocytes. FEBS Let 195:106–110
Morel F (1981) Sites of hormone action in the mammalian nephron. Am J. Physiol 240:F159-F164
Morel F, Chabardès D, Imbert-Teboul M, Le Bouffant F, HusCitharel A, Montégut M (1982) Multiple hormonal control of adenylate-cyclase in distal segments of the rat kidney. Kidney Int 21:S55-S62
Nitschke R, Fröbe U, Greger R (1991) Antidiuretic hormone acts via V1 receptors on intracellular calcium in the isolated perfused rabbit cortical thick ascending limb. Pflügers Arch 417:622–632
Rosenthal W, Hescheler J, Trautwein W, Schultz G (1988) Control of voltage-dependent Ca2+ channels by G proteincoupled receptors. FASEB J 2:1784–1790
Rouffignac C de, Elalouf JM, Roinel N, Bailly C, Amiel C (1984) Similarity of the effects of antidiuretic hormone, parathyroid hormone, calcitonin, and glucagon or rat kidney. In: Robinson RR (ed) Nephrology. Springer, Berlin Heidelberg New York, pp 340–357
Rouffignac C de, Di Stefano A, Wittner M, Roinel N, Elalouf JM (1991) Consequences of differential effects of ADH and other peptide hormones on thick ascending limbs of mammalian kidney. Am J Physiol 260:R1023-R1035
Schiebinger RJ, Braley LM, Menachery A, Williams GH (1985) Calcium, a “third messenger” of cAMP-stimulated adrenal steroid secretion. Am J Physiol 248:E89-E94
Takemura H, Hughes AR, Thastrup O, Putney JW Jr (1989) Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells: evidence that an intracellular calcium pool, and not an inositol phosphate, regulates calcium fluxes at the plasma membrane. J Biol Chem 264:12266–12271
Tan YP, Marty A (1991) Protein kinase C-mediated desensitization of the muscarinic response in rat lacrimal gland cells. J Physiol (Lond) 433:357–371
Taniguchi S, Marchetti J, Morel F (1989) Cytosolic free calcium in single microdissected rat cortical collecting tubules. Pflügers Arch 414:125–133
Thastrup O, Cullen PJ, Drobak B, Hanley MR, Dawson AP (1990) Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc Natl Acad Sci USA 87:2466–2470
Uneyama H, Uneyama C, Akaike N (1933) Intracellular mechanisms of cytoplasmic Ca2+ oscillation in rat megakaryocyte. J Biol Chem 268:168–174
Willems PHGM, Van Den Brock BAM, Van Os CH, De Pont JJHHM (1989) Inhibition of inositol 1,4,5-triphosphate-induced Ca2+ release in permeabilized pancreatic acinar cells hy hormonal and phorbol ester pretreatment. J Biol Chem 264:9762–9767
Wittner M, Di Stefano A, Wangemann P, Nitschke R, Greger R, Bailly C, Amiel C, Roinel N, de Rouffignac C (1988) Different effects of ADH on sodium, chloride, potassium, calcium, and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron. Pflügers Arch 412: 516–523
Wittner M, Di Stefano A, Mandon B, Roinel N, de Rouffignac C (1991) Stimulation of NaCl reabsorption by antidiuretic hormone in the cortical thick ascending limb of Henle's loop of the mouse. Pflügers Arch 419:212–214
Woods NM, Cuthbertson KSR, Cobbold PTS (1987) Phorbolester-induced alterations of free calcium ion transients in single rat hepatocytes. Biochem J 246:619–623
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Dai, L.J., Quamme, G.A. Hormone-mediated Ca2+ transients in isolated renal cortical thick ascending limb cells. Pflügers Arch. 427, 1–8 (1994). https://doi.org/10.1007/BF00585935
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DOI: https://doi.org/10.1007/BF00585935