The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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P2 Receptor-mediated Inhibition of Vasopressin-stimulated Fluid Transport and cAMP Responses in AQP2-transfected MDCK Cells

  • Kim, Yang-Hoo (Department of Physiology, Pusan National University School of Medicine) ;
  • Choi, Young-Jin (Department of Physiology, Pusan National University School of Medicine) ;
  • Bae, Hae-Rahn (Department of Physiology, Dong-A University College of Medicine) ;
  • Woo, Jae-Suk (Department of Physiology, Pusan National University School of Medicine)
  • Published : 2009.02.28
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Abstract

We cultured canine kidney(MDCK) cells stably expressing aquaporin-2(AQP2) on collagen-coated permeable membrane filters and examined the effect of extracellular ATP on arginine vasopressin(AVP)-stimulated fluid transport and cAMP production. Exposure of cell monolayers to basolateral AVP resulted in stimulation of apical to basolateral net fluid transport driven by osmotic gradient which was formed by addition of 500 mM mannitol to basolateral bathing solution. Pre-exposure of the basolateral surface of cell monolayers to ATP(100 ${\mu}M$) for 30 min significantly inhibited the AVP-stimulated net fluid transport. In these cells, AVP-stimulated cAMP production was suppressed as well. Profile of the effects of different nucleotides suggested that the $P2Y_2$ receptor is involved in the action of ATP. ATP inhibited the effect of isoproterenol as well, but not that of forskolin to stimulate cAMP production. The inhibitory effect of ATP on AVP-stimulated fluid movement was attenuated by a protein kinase C inhibitor, calphostin C or pertussis toxin. These results suggest that prolonged activation of the P2 receptors inhibits AVP-stimulated fluid transport and cAMP responses in AQP2 transfected MDCK cells. Depressed responsiveness of the adenylyl cyclase by PKC-mediated modification of the pertussis-toxin sensitive $G_i$ protein seems to be the underlyihng mechanism.

Keywords

References

  1. Andersen-Beckh B, Dehe M, Schülein R, Wiesner B, Rutz C, Liebenhoff U, Rosenthal W, Oksche A. Polarized expression of the vasopressin V2 receptor in Madin-Darby canine kidney cells. Kidney Int 56: 517-527, 1999 https://doi.org/10.1046/j.1523-1755.1999.00569.x
  2. Beckner SK, Farrar WL. Inhibition of adenylate cyclase by IL 2 in human T lymphocytes is mediated by protein kinase C. Biochem Biophys Res Commun 145: 176-182, 1987 https://doi.org/10.1016/0006-291X(87)91303-9
  3. Budnik LT, Mukhopadhyay AK. Desensitisation of LH-stimulated cyclic AMP accumulation in isolated bovine luteal cells-effect of phorbol ester. Mol Cell Endocrinol 54: 51-61, 1987 https://doi.org/10.1016/0303-7207(87)90139-0
  4. Buhl AM, Sheikh MI, Steensgaard J, Roigaard-Petersen H, Jacobsen C. GTP-binding proteins in luminal and basolateral membranes from pars convoluta and pars recta of rabbit kidney proximal tubule. FEBS Lett 304: 179-183, 1992 https://doi.org/10.1016/0014-5793(92)80613-L
  5. Deen PM, Rijss JP, Mulders SM, Errington RJ, Van Baal J, Van Os CH. Aquaporin-2 transfection of Madin–Darby canine kidney cells reconstitutes AVP-regulated transcellular osmotic water transport. J Am Soc Nephrol 8: 1493-1501, 1997
  6. Dubyak GR, El-Moatassim C. Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. Am J Physiol 265: C577-C606, 1993 https://doi.org/10.1152/ajpcell.1993.265.3.C577
  7. Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M. Towards a revised nomenclature for P1 and P2 receptors. Trends Pharmacol Sci 18: 79-82, 1997 https://doi.org/10.1016/S0165-6147(96)01038-3
  8. Harden TK, Boyer JL, Nicholas RA. P2-purinergic receptors: subtype-ssociated signaling responses and structure. Annu Rev Pharmacol Toxicol 35: 541-579, 1995 https://doi.org/10.1146/annurev.pa.35.040195.002545
  9. Heilbronn E, Knoblauch BH, Muller CE. Uridine nucleotide receptors and their ligands: structural, physiological, and pathophysiological aspects, with special emphasis on the nervous system. Neurochem Res 22: 1041-1050, 1997 https://doi.org/10.1023/A:1022487128766
  10. Kishore BK, Ginns SM, Krane CM, Nielsen S, Knepper MA. Cellular localization of P2Y2 purinoceptor in rat renal inner medulla and lung. Am J Physiol 278: F43-F51, 2000
  11. Knepper MA. Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am J Physiol 272: F3-F12, 1997
  12. Kobayashi E, Nakano H, Morimoto M, Tamaoki T. Calphostin C (UCN-1208C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 159: 548-553, 1989 https://doi.org/10.1016/0006-291X(89)90028-4
  13. Lin WW, Chuang DD. Endothelin- and ATP-induced inhibition of adenylyl cyclase activity in C6 glioma cells: Role of Gi and calcium. Mol Pharmacol 44: 158-165, 1993
  14. McCoy DE, Taylor AL, Kudlow BA, Karlson K, Slattery MJ, Schwiebert LM, Schwiebert EM, Stanton BA. Nucleotides regulate NaCl transport in mIMCD-K2 cells via P2X and P2Y purinergic receptors. Am J Physiol 277: F552-F559, 1999
  15. North RA, Barnard EA. Nucleotide receptors. Curr Opin Neurobiol 7: 346-357, 1997 https://doi.org/10.1016/S0959-4388(97)80062-1
  16. Okajima F, Tokumitsu Y, Kondo Y, Ui M. P2-purinergic receptors are coupled to two signal transduction systems leading to inhibition of cAMP generation and to production of inositol triphosphate in rat hepatocytes. J Biol Chem 262: 13483-13490, 1987
  17. Pianet I, Merle M, Labouesse J. ADP and indirectly, ATP are potent inhibitors of cAMP production in intact isoproterenol- stimulated C6 glioma cells. Biochem Biophys Res Commun 163: 1150-1157, 1989 https://doi.org/10.1016/0006-291X(89)92341-3
  18. Post SR, Jacobson JP, Insel PA. P2 purinergic receptor agonists enhance cAMP production in Mardin-Darby canine kidney epithelial cells via autocrine/paracrine mechanism. J Biol Chem 271: 2029-2032, 1996 https://doi.org/10.1074/jbc.271.4.2029
  19. Post SR, Rump LC, Zambon A, Hughes RJ, Buda MD, Jacobson JP, Kao CC, Insel PA. ATP activates cAMP production via multiple purinergic receptors in MDCK-D1 epithelial cells. Blockade of an autocrine/paracrine pathway to define receptor preference of an agonist. J Biol Chem 273: 23093-23097, 1998 https://doi.org/10.1074/jbc.273.36.23093
  20. Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, Vallon V. Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal $Na^+$ and water reabsorption. FASEB J 21: 3717-3726, 2007 https://doi.org/10.1096/fj.07-8807com
  21. Sato K, Okajima F, Kondo Y. Extracellular ATP stimulates three different receptor-signal transduction systems in FRTL-5 thyroid cells. Biochem J 283: 282-287, 1992
  22. Teitelbaum I. Protein kinase C inhibits arginine vasopressin- stimulated cAMP accumulation via a Gi-dependent mechanism. Am J Physiol 264: F216-220, 1993
  23. Vallon V. P2 receptors in the regulation of renal transport mechanisms. Am J Physiol 294: F10-F27, 2008
  24. Williams M, Burnstock G. Purinergic neurotransmission and neuromodulation: a historical perspective. In: Jacobson KA, Jarvis MF ed, Purinergic Approaches in Experimental Therapeutics. 1st ed. Wiley-Liss, Inc, New York, p 3-26, 1997
  25. Woo JS, Inoue CN, Hanaoka K, Schwiebert EM, Guggino SE, Guggino WB. Adenylyl cyclase is involved in desensitization and recovery of ATP-stimulated Cl- secretion in MDCK cells. Am J Physiol 274: C371-C378, 1998 https://doi.org/10.1152/ajpcell.1998.274.2.C371
  26. Yamada M, Hamamori Y, Akita H, Yokoyama M. P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes. Circ Res 70: 477-485, 1992