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Characterization of ANF-R2 receptor-mediated inhibition of adenylate cyclase

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Abstract

We have characterized the ANF-R2 receptor-mediated inhibition of adenylate cyclase with respect to its modulation by several regulators. ANF (99–126) inhibits adenylate cyclase activity only in the presence of guanine nucleotides. The maximal inhibition (∼ 45%) was observed in the presence of 10-30 μM GTPγS, and at higher concentrations, the inhibitory effect of ANF was completely abolished. ANF-mediated inhibition was not dependent on the presence of monovalent cations, however Na+ enhanced the degree of inhibition by about 60%, whereas K+ and Li+ suppressed the extent of inhibition by about 50%. On the other hand, divalent cation, such as Mn2+ decreased the degree of inhibition in a concentration dependent manner, with an apparent Ki of about 0.7 mM, and at 2 mM; the inhibition was completely abolished. In addition, proteolytic digestion of the membranes with trypsin (40 ng/ml) resulted in the attenuation of ANF-mediated inhibition of adenylate cyclase. Other membrane disrupting agents such as neuraminidase and phospholipase A2 treatments also inhibited completely, the ANF-mediated inhibition of enzyme activity. N-Ethylmaleimide (NEM), phorbol ester and Ca2+-phospholipid dependent protein kinase (C-kinase) which have been shown to interact with inhibitory guanine nucleotide regulating protein (Gi) also resulted in the attenuation of ANF-mediated inhibition of adenylate cyclase activity. These results indicate that in addition to the Gi, the phospholipids and glycoproteins may also play an important role in the expression of ANF-R2 receptor-mediated inhibition of adenylate cyclase.

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Abbreviations

ANF:

Atrial Natriuretic Factor

GTPγS:

Guanosine 5′-0-(Thiotriphosphate)

Gi:

inhibitory guanine nucleotide regulatory protein

NEM:

N-Ethylmaleimide

PMA:

Phorbol, 12-Myristate, 13-Acetate, C-kinase, Ca 2+, phospholipid-dependent protein kinase

PHL-A2 :

Phospholipase A,

References

  1. Cantin M, Genest J: The heart as an endocrine gland. Endocr Rev 6: 107–127, 1985

    Google Scholar 

  2. Waldman SA, Rapport RM, Murad F: Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem 259: 14332–14334, 1984

    Google Scholar 

  3. Tremblay J, Gerzer R, Vinay P, Pang SC, Béliveau R, Hamet P: The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase. FEBS Lett 181: 17–22, 1985

    Google Scholar 

  4. Anand-Srivastava MB, Franks DJ, Cantin M, Genest J: Atrial natriuretic factor inhibits adenylate cyclase activity. Biochem Biophys Res Commun 121: 855–862, 1984

    Google Scholar 

  5. Ishikawa S, Saito T, Okada K, Kuzuya T, Kangawa K, Matsuo H: Atrial natriuretic factor increases cyclic GMP and inhibits cyclic AMP in rat renal papillary collecting tubule cells in culture. Biochem Biophys Res Commun 130: 1147–1153, 1985

    Google Scholar 

  6. Barrett PQ, Isales CM: The role of cyclic nucleotides in atrial natriuretic peptide-mediated inhibition of aldosterone secretion. Endocrinology 122: 799–808, 1988

    Google Scholar 

  7. Anand-Srivastava MB, Vinay P, Genest J, Cantin M: Effect of atrial natriuretic factor on adenylate cyclase in various nephron segments. Am J Physiol 251: F417-F423, 1986

    Google Scholar 

  8. Anand-Srivastava MB, Cantin M: Atrial natriuretic factor receptors are negatively coupled to adenylate cyclase in cultured atrial and ventricular cardiocytes. Biochem Biophys Res Commun 138: 427–436, 1986

    Google Scholar 

  9. Anand-Srivastava MB, Cantin M, Genest J: Inhibition of pitituary adenylate cyclase by atrial natiuretic factor. Life Sci 36: 1873–1879, 1985

    Google Scholar 

  10. Anand-Srivastava MB, Genest J, Cantin M: Inhibitory effect of atrial natriuretic factor on adenylate cyclase activity in adrenal cortical membranes. FEBS Lett 181: 199–202, 1985

    Google Scholar 

  11. Bianchi C, Anand-Srivastava MB, de Lean A, Gutkowska J, Forthomme D, Genest J, Cantin M: Localization and characterization of specific receptors for atrial natriuretic factor in the ciliary processes of the eye. Current Eye Res 5: 283–293, 1986

    Google Scholar 

  12. Leitman D, Anderson JW, Kuno T, Kamisaki Y, Chang JK, Murad F: Identification of multiple binding sites for atrial natriuretic factor by affinity cross-linking in culture endothelial cells. J Biol Chem 261: 11650–11655, 1986

    Google Scholar 

  13. Takayanagi R, Inagami T, Snajdar RM, Imada T, Tamura M, Misono KS: Two distinct forms of receptors for atrial natriuretic factor in bovine adrenocortical cells: Purification, ligand binding, and peptide mapping. J Biol Chem 262: 12104–12113, 1987

    Google Scholar 

  14. Leitman D, Anderson JW, Catalano RM, Waldman SA, Tuan JJ, Murad F: Atrial natriuretic peptide binding, cross-linking, and stimulation of cyclic GMP accumulation and particulate guanylate cyclase activity in cultured cells. J Biol Chem 263: 3720–3728, 1988

    Google Scholar 

  15. Ricard B, Fourguet P, Massacrier A, Courand F: Photoaffinity labeling of ANF receptor in cultured brain neurones. Biochem Biophys Res Commun 152: 1031–1037, 1988

    Google Scholar 

  16. Clinkers M, Garbers DL, Chang MS, Lowe DG, Chin H, Goeddel DV, Schultz S: A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor. Nature 338: 78–83, 1989

    Google Scholar 

  17. Schultz S, Singh S, Bellet RA, Singh G, Tubb DJ, Chin H, Garbers DL: The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family. Cell 58: 1155–1162, 1989

    Google Scholar 

  18. Chang M, Lowe DG, Lewis M, Hellariss R, Chen E, Goeddel DV: Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate eyclases. Nature 341: 68–72, 1989

    Google Scholar 

  19. Fuller F, Porter JG, Arfsten AE, Miller J, Schilling TW, Scarborough RM, Lewicki JA, Schenk DB: Atria( natriuretic peptide clearance receptor: complete sequence and functional expression of cDNA clones. J Biol Chem 263: 9395–9401, 1988

    Google Scholar 

  20. Maack T, Suzuki M, Almeida FA, Nussenzeig D, Scarborough RM, McEnroe GA, Lewicki JA: Physiological role of silent receptors of atrial natriuretic factor. Science 238: 675–678, 1987

    Google Scholar 

  21. Anand-Srivastava MB, Srivastava AK, Cantin M: Pertussis toxin attenuates atrial natriuretic factor-mediated inhibition of adenylate cyclase: involvement of inhibitory guanine nucleotide regulatory protein. J Biol Chem 262: 4931–4934, 1987

    Google Scholar 

  22. Resink TJ, Panchenko MP, Trachuk VA, Buhler FR: Involvement of Ni protein in the functional coupling of the atrial natriuretic factor (ANF) receptor to adenylate cyclase in rat lung plasma membranes. Eur J Biochem 174: 531–535, 1988

    Google Scholar 

  23. Anand-Srivastava MB, Sairam MR, Cantin M: Ring-deleted analogs of atrial natriuretic factor inhibit adenylate cyclase/cAMP system. Possible coupling of clearance atrial natriuretic factor receptors to adenylate cyclase/CAMP signal transduction system. J Biol Chem 265: 8566–8572, 1990

    Google Scholar 

  24. Drewett JG, Ziegler RJ, Trachte CJ: Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells. J Pharmacol Expt Therap 255: 497–503, 1990

    Google Scholar 

  25. Katada T, Gilman AH, Watanabe Y, Banes S, Jakobs KH: Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem 151: 431–437, 1985

    Google Scholar 

  26. Anand-Srivastava MB, Srivastava AK: Modulation of adenylate cyclase activity by Ca2+, phospholipid-dependent protein kinase in rat brain striatum. Mol Cell Biochem 92: 91–98, 1990

    Google Scholar 

  27. Kitamura Y, Nomura Y: Uncoupling of rat cerebral cortical α2-adrenoceptors from GTP-binding proteins by N-ethylmaleimide. J Neurochem 49: 1894–1901, 1987

    Google Scholar 

  28. Salomon Y, Londos C, Rodbell M: A highly sensitive adenylate cyclase assay. Anal Biochem 58: 541–548, 1974

    Google Scholar 

  29. Heisler S, Simard J, Assayag E, Mehri Y, Labrie F: Atrial natriuretic factor does not affect basal, forskolin- and CRF stimulated adenylate cyclase activity, cAMP formation or ACTH secretion, but does stimulate cGMP synthesis in anterior pituitary. Mol Cell Endocrinol 44: 125–131, 1986

    Google Scholar 

  30. Jakobs KH, Aktories K, Minuth M, Schultz G: Inhibition of adenylate cyclase. Adv Cyclic Nucleotide Res 19: 137–150, 1985

    Google Scholar 

  31. Limbird LE, Speck JL, Smith SK: Sodium ion modulates agonist and antagonist interactions with the human platelet Alpha2-adre-nergic receptor in membrane and solubilized preparations. Mol Pharmacol 21: 609–617, 1982

    Google Scholar 

  32. Avissar S, Schreiber G, Danon A, Belmaker RH: Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex. Nature 331: 440–442, 1988

    Google Scholar 

  33. Garbers DL, Johnson RA: Metal and metal-ATP interactions with brain and cardiac adenylate eyclases. J Biol Chem 250: 8449–8456, 1975

    Google Scholar 

  34. Jackowski MM, Johnson RA, Exton JH: Calcium regulation of guanine nucleotide activation of hepatic adenylate cyclase. Biochim Biophys Acta 630: 497–510, 1980

    Google Scholar 

  35. Anand-Srivastava MB: Regulation of adenylate cyclase by adenosine and other agonists in rat myocardial sarcolemma. Arch Biochem Biophys 243: 439–446, 1985

    Google Scholar 

  36. Anand-Srivastava MB, Franks DJ, Cantin M, Genest J: Presence of ‘Ra’ and ‘P’-site receptors for adenosine coupled to adenylate cyclase in cultured vascular smooth muscle cells. Biochem Biophys Res Commun 108: 213–219, 1982

    Google Scholar 

  37. Limbird LE, Lefkowitz RJ: Adenylate-cyclase coupled Beta adrenergic receptors: effect of membrane lipid — perturbing agents on receptor binding and enzyme stimulation by catecholamines. Mol Pharmacol 12: 559–567, 1976

    Google Scholar 

  38. Stengel D, Lad PM, Nielsen TB, Rodbell M, Hanoune J: Proteolysis activates adenylate cyclase in rat liver and AC lymphoma cell independently of the guanine nucleotide regulatory site. FEBS Lett 115: 260–264, 1980

    Google Scholar 

  39. Friedman Y, Wilger J, Crowell D, Burke G: Effects of proteolytic enzymes and protease inhibitors on bovine thyroid adenylate cyclase activity. Endocrinology 112: 1674–1679, 1983

    Google Scholar 

  40. Anderson WB, Jaworski CJ, Vlahakis G: Proteolytic activation of adenylate cyclase form cultured fibroblasts. J Biol Chem 253: 2921–2926, 1978

    Google Scholar 

  41. Stiles GL, Lefkowitz RJ: Hormone-sensitive adenylate cyclase: delineation of a trypsin-sensitive site in the pathway of receptor-mediated inhibition. J Biol Chem 257: 6287–6291, 1982

    Google Scholar 

  42. Liu B, Meloche S, McNicoll N, Lord C, De Lean A: Topographical characterization of the domain structure of the bovine adrenal atrial natriuretic factor R1 receptor. Biochem 28: 5599–5605, 1989

    Google Scholar 

  43. Larsen NE, Mullikin-Kilpatrick D, Blume AJ: Two different modifications of the neuroblastoma × glioma hybrid opiate receptors induced by N-ethylmaleimide. Mol Pharmacol 20: 255–262, 1981

    Google Scholar 

  44. Waldman SA, Rapport RM, Fiscus RR, Murad F: Effects of atriopeptin on particulate guanylate cyclase from rat adrenal. Biochem Biophys Acta 845: 298–303, 1985

    Google Scholar 

  45. Yip CC, Laing LP, Flynn TG: Photoaffinity labeling of atrial natriuretic factor receptors of rad kidney cortex plasma membranes. J Biol Chem 260: 8229–8232, 1985

    Google Scholar 

  46. Lefkowitz RJ: Catecholamine stimulated myocardial adenylate cyclase: effects of phospholipase digestion and the role of membrane lipids. J Mol Cell Cardiol 7: 27–37, 1975

    Google Scholar 

  47. Levey GS: Restoration of norepinephrine responsiveness of solubilized myocardial adenylate cyclase by phosphatidylinositol. J Biol Chem 246: 7405–7410, 1971

    Google Scholar 

  48. Anand-Srivastava MB, Johnson RA: Role of phospholipids in coupling of adenosine and dopamine receptors to striatal adenylate cyclase. J Neurochem 36: 1819–1828, 1981

    Google Scholar 

  49. Azhar S, Hajra M, Menon KMJ: Gonadotropin receptors in plasma membranes of bovine corpus luteum: II Role of membrane phospholipids. J Biol Chem 251: 7405–7412, 1976

    Google Scholar 

  50. Castagna M, Takai Y, Kaibuch K, Sano K, Kikkawa U, Nishizuka Y: Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257: 7847–7851, 1982

    Google Scholar 

  51. Katada T, Ui M: ADP ribosylation of the specific membrane protein of C6 cells by Islet-activating protein associated with modification of adenylate cyclase activity. J Biol Chem 257: 7210–7216, 1982

    Google Scholar 

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  1. Département de physiologic, Faculté de Médecine, Université de Montréal, Succursale A, C.P. 6128, H3C3J7, Montreal, Québec, Canada

    Madhu B. Anand-Srivastava

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Anand-Srivastava, M.B. Characterization of ANF-R2 receptor-mediated inhibition of adenylate cyclase. Mol Cell Biochem 113, 83–92 (1992). https://doi.org/10.1007/BF00230889

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  • DOI: https://doi.org/10.1007/BF00230889

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