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Endothelin Regulation of Cardiac Contractility: Signal Transduction Pathways

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Endothelin Receptors and Signaling Mechanisms

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Abstract

When the discovery of endothelin (ET) was first reported in 1988, it was described as a potent vasoconstrictor.1 Subsequent studies have further charac-terized the effects of the peptide on cardiovascular contractility. It has been shown both in the vasculature and in myocardial preparations that ET stimulation triggers a maintained contraction which is difficult to reverse.2–5 Since the first reports of ET action on contractility, genes for three endothelins, ET1, ET2 and ET3, and at least two classes of ET cell surface receptors, ETA and ETB, expressed in a tissue-specific manner, have been identified.2,6 One or more of these related family of peptides is present in virtually all tissues and in all mammalian species.6 Not only do ETs play important physiological roles in smooth and cardiac muscle contraction, but they are also implicated in kidney function, in neurotransmission and in the regulation of development. New functions of the peptide continue to be reported.

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References

  1. Yanagisawa M, Kurihara H, Kimura S et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332(31)411–415.

    Google Scholar 

  2. Masaki T, Yanagisawa M. Physiology and pharmacology of endothelins. Medicinal Res Rev 1992; 12 (4): 391–421.

    Article  CAS  Google Scholar 

  3. Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev 1994; 46 (3): 325–414.

    PubMed  CAS  Google Scholar 

  4. Simonson MS. Endothelins: multifunctional renal peptides. Physiol Rev 1993; 73: 375–411.

    PubMed  CAS  Google Scholar 

  5. Grossman JD, Morgan JP. Cardiovascular effects of endothelin. News Physiol Sci 1997; 12: 113–117.

    CAS  Google Scholar 

  6. Sokolovsky M. Endothelin receptor heterogeneity, G-proteins, and signaling via cAMP and cGMP cascades. Cell Mol Neurobiol 1995; 15 (5): 561–571.

    Article  PubMed  CAS  Google Scholar 

  7. Hasdai D, Kornowski R, Battler A. Endothelin and myocardial ischemia. Cardiovasc Drugs Ther 1994; 8: 589–599.

    Article  PubMed  CAS  Google Scholar 

  8. Schiffrin EL. Endothelin in hypertension. Curr Opin Cardiol 1995; 10485–494.

    Google Scholar 

  9. Löscher TF, Seo B, Bühler FR. Potential role of endothelin in hypertension. Hypertension 1993; 21(6)752–757.

    Google Scholar 

  10. Vanhoutte PM. Is endothelin involved in the pathogenesis of hypertension? Hypertension 1993; 21 (6): 747–751.

    Article  PubMed  CAS  Google Scholar 

  11. Moravec CS, Reynolds EE, Stewart RW et al. Endothelin is a positive inotropic agent in human and rat heart in vitro. Biochem Biophys Res Commun 1989; 159 (1): 14–18.

    Article  Google Scholar 

  12. Watanabe T, Kusumoto K, Kitayoshi et al. Positive inotropic and vasoconstrictive effects of endothelin-i in in vivo and in vitro experiments: characteristics and the role of L-type calcium channels. J Cardiovasc Pharmacol 1989; 13 (Suppl 5): S108–5111.

    Article  PubMed  CAS  Google Scholar 

  13. Endoh M, Norota I, Yang H et al. The positive inotropic effect and the hydrolysis of phosphoinositide induced by endothelin-3 in rabbit ventricular myocardium: inhibition by a selective antagonist of ETA receptors, FR139317. J Pharmacol Exp Ther 1996; 277 (1): 61–70.

    PubMed  CAS  Google Scholar 

  14. Ishikawa T, Yanagisawa M, Kimura S et al. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. Am J Physiol 1988; 255: H970 - H973.

    PubMed  CAS  Google Scholar 

  15. Reid JJ, Lieu At, Rand MJ. Interactions between endothelin-i and other chrono-tropic agents in rat isolated atria. Eur J Pharmacol 1991; 194: 173–181.

    Article  PubMed  CAS  Google Scholar 

  16. Krämer BK, Nishida M, Kelly RA et al. Myocardial actions of a new class of cytokines. Circulation 1992; 85 (1): 35o - 356.

    Article  Google Scholar 

  17. Kelly RA, Eid H, Krämer BK et al. Endothelin enhances the contractile responsiveness of adult rat ventricular myocytes to calcium by a pertussis toxin-sensitive pathway. J Clin Invest 1990; 86: 1164–1171.

    Article  PubMed  CAS  Google Scholar 

  18. Krämer BK, Smith TW, Kelly RA. Endothelin and increased contractility in adult rat ventricular myocytes. Circ Res 1991; 68 (1): 269–279.

    Article  PubMed  Google Scholar 

  19. Kohmoto O, Ikenouchi H, Hirata Y et al. Variable effects of endothelin-1 on [Ca2+]i transients, pH;, and contraction in ventricular myocytes. Am J Physiol 1993; 265: H793 - H800.

    PubMed  CAS  Google Scholar 

  20. Damron DS, Darvish A, Murphy L et al. Arachidonic acid-dependent phosphorylation of troponin I and myosin light chain 2 in cardiac myocytes. Circ Res 1995; 76(6)ao11–1o19.

    Google Scholar 

  21. Fujita S, Endoh M. Effects of endothelin-1 on [Ca2+];-shortening trajectory and Ca2+ sensitivity in rabbit single ventricular cardiomyocytes loaded with indo-1/AM: comparison with the effects of phenylephrine and angiotensin II. J Card Fail 1996; 2(4S)S45–S57.

    Google Scholar 

  22. Ishikawa T, Liming L, Shinmi O et al. Characteristics of binding of endothelin-1 and endothelin-3 to rat hearts. Developmental changes in mechanical responses and receptor subtypes. 1991; Circ Res 69(4)918–926.

    Google Scholar 

  23. Jiang T, Pak E, Zhang H. Endothelin-dependent actions in cultured AT-1 cardiac myocytes. The: role of the a isoform of protein kinase C. Circ Res 1996; 78(4)724–736.

    Google Scholar 

  24. Li K, Stewart DJ, Rouleau J. Myocardial contractile actions of endothelin-i in rat and rabbit papillary muscles. Role of endocardial endothelium. Circ Res 1991; 69(2)301–312.

    Google Scholar 

  25. Mebazaa A, Mayoux E, Maeda K et al. Paracrine effects of endocardial endothelial cells on myocyte contraction mediated via endothelin. Am J Physiol 1993; 265: H1841 - H1846.

    PubMed  CAS  Google Scholar 

  26. Suzuki T, Kumazaki T, Mitsui Y. Endothelin-1 is produced and secreted by neonatal rat cardiac myocytes in vitro. Biochem Biophys Res Comm 1993; 191 (3): 823–830.

    Article  PubMed  CAS  Google Scholar 

  27. Baydoun AR, Peers SH, Cirino G et al. Effects of endothelin-i on the rat isolated heart. J Cardiovasc Pharmacol 1989; 13 (Suppl 5): S193 - S196.

    Article  PubMed  CAS  Google Scholar 

  28. Firth JD, Roberts AFC, Raine AEG. Effect of endothelin on the function of the isolated perfused working rat heart. Clin Sci 1990; 79: 221–226.

    PubMed  CAS  Google Scholar 

  29. Shah AM, Lewis MJ, Henderson AH. Inotropic effects of endothelin in ferret ventricular myocardium. Eur J Pharmacol 1989; 163: 365–367.

    Article  PubMed  CAS  Google Scholar 

  30. Wang J, Paik G, Morgan JP. Endothelin 1 enhances myofilament Ca2+ responsiveness in aequorin-loaded ferret myocardium. Circ Res 1991; 69 (3): 582–589.

    Article  PubMed  CAS  Google Scholar 

  31. Highsmith RF, Blackburn K, Schmidt DJ. Endothelin and calcium dynamics in vascular smooth muscle. Ann Rev Physiol 1992; 54: 257–277.

    Article  CAS  Google Scholar 

  32. Lauer MR, Gunn MD, Clusin WT. Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes. J Physiol 1992; 448: 729–747.

    PubMed  CAS  Google Scholar 

  33. Vigne P, Lazdunski M, Frelin C. The inotropic effect of endothelin-i on rat atria involves hydrolysis of phosphatidylinositol. FEBS Lett 1989; 249(2)143–146.

    Google Scholar 

  34. Stewart DJ, Cernacek P, Costello KB et al. Elevated endothelin 1 in heart failure and loss of normal response to postural change. Circulation 1992; 85510–517.

    Google Scholar 

  35. Cavero PG, Miller WL, Heublein DM et al. Endothelin in experimental congestive heart failure in the anesthetized dog. Am J Physiol 1990; 259: F312 - F317.

    PubMed  CAS  Google Scholar 

  36. Lerman A, Hildebrand FL, Aarhus LL et al. Endothelin has biological actions at pathophysiological concentrations. Circulation 1991; 83: 1808–1814.

    Article  PubMed  CAS  Google Scholar 

  37. Arai H, Hon S, Aramori I et al. Cloning and expression of a cDNA encoding an endothelin receptor. Nature 1990; 348: 730–732.

    Article  PubMed  CAS  Google Scholar 

  38. Cyr C, Heubner K, Druck T et al. Cloning and chromosomal localization of a human endothelin EA receptor. Biochem Biophys Res Comm 1991; 181: 184–190.

    Article  PubMed  CAS  Google Scholar 

  39. Sakurai T, Yanagisawa M, Takuwa Y et al. Cloning of a cDNA encoding a nonisopeptide-selective subtype of the endothelin receptor. Nature 1990; 348: 732–735.

    Article  PubMed  CAS  Google Scholar 

  40. Aramori I, Nakanishi S. Coupling of two endothelin receptor subtypes to differing signal transduction in transfected Chinese hamster ovary cells. J Biol Chem 1992; 267 (18): 12468–12474.

    PubMed  CAS  Google Scholar 

  41. Molenaar P, O’Reilly G, Sharkey A et al. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res 1993; 72(3)526–538.

    Google Scholar 

  42. Hilal-Dandan R, Merck DT, Lujan JP et al. Coupling of the type A endothelin receptor to multiple responses in adult rat cardiac myocytes. Mol Pharmacol 1994; 45 (6): 1183–1190.

    PubMed  CAS  Google Scholar 

  43. Hilal-Dandan R, Ramirez MT, Villegas S et al. Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways. Am J Physiol 1997; 272 (1): H130 - H137.

    PubMed  CAS  Google Scholar 

  44. Ono K, Eto K, Sakamoto A et al. Negative chronotropic effect of endothelin 1 mediated through ETA receptor in guinea pig atria. Circ Res 1995; 76 (2): 284–292.

    Article  PubMed  CAS  Google Scholar 

  45. Dohlman HG, Caron MG, Lefkowitz RJ. A family of receptors coupled to guanine nucleotide regulatory proteins. Biochemistry 1987; 26: 2657–2664.

    Article  PubMed  CAS  Google Scholar 

  46. Takuwa Y, Kasuya Y, Takuwa N et al. Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide regulatory binding regulatory protein in vascular smooth muscle cells. J Clin Invest 1990; 85: 653–658.

    Article  PubMed  CAS  Google Scholar 

  47. Thomas CP, Kester M, Dunn MJ. A pertussis toxin-sensitive GTP-binding protein couples endothelin to phospholipase C in rat mesangial cells. Am J Physiol 1991; 260: F347 - F352.

    PubMed  CAS  Google Scholar 

  48. Berstein G, Blank JL, Smrcka AV et al. Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-beta 1. J Biol Chem 1992; 267: 8081–8088.

    PubMed  CAS  Google Scholar 

  49. Camps M, Carozzi A, Schnabel P. Isozyme-selective stimulation of phospholipase C-(32 by G protein 13y-subunits. Nature 1992; 360: 684–686.

    Article  PubMed  CAS  Google Scholar 

  50. Katz A, Wu D. Simon MI. Subunits 3y of heterotrimeric G protein activate (32 isoform of phospholipase C. Nature 1992; 360: 686–689.

    Article  PubMed  CAS  Google Scholar 

  51. Takigawa M, Sakurai T, Kasuya Y et al. Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. Eur J Biochem 1995; 228: 102–108.

    Article  PubMed  CAS  Google Scholar 

  52. Marsden PA, Danthuluri NR, Brenner BM et al. Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization. Biochem Biophys Res Commun 1989; 158: 86–93.

    Article  PubMed  CAS  Google Scholar 

  53. Griendling KK, Tsuda T, Alexander RW. Endothelin stimulates diacylglycerol accumulation and activates protein kinase C in cultured vascular smooth muscle cells. J Biol Chem 1989; 264: 8237–8240.

    PubMed  CAS  Google Scholar 

  54. Simonson MS, Wann S, Mene P et al. Endothelin stimulates phospholipase C, Na+-H* exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest 1989; 83: 708–712.

    Article  PubMed  CAS  Google Scholar 

  55. Muldoon L, Rodland KD, Forsythe ML et al. Stimulation of phosphatidylinositol hydrolysis, diacylglycerol release, and gene expression in response to endothelin, a potent new agonist for fibroblasts and smooth muscle cells. J Biol Chem 1989; 264: 8529–8536.

    PubMed  CAS  Google Scholar 

  56. Galron R, Kloog Y, Bdolah A et al. Functional endothelin/sarafotoxin receptors in rat heart myocytes: structure-activity relationships and receptor subtypes. Biochem Biophys Res Comm 1989; 163: 936–943.

    Article  PubMed  CAS  Google Scholar 

  57. Takanashi M, Endoh M. Concentration-and time-dependence of phosphoinositide hydrolysis induced by endothelin-1 in relation to the positive inotropic effect in the rabbit ventricular myocardium. J Pharmacol Exp Ther 1992; 262 (3): 1189–1194.

    PubMed  CAS  Google Scholar 

  58. Prasad MR. Endothelin stimulates degradation of phospholipids in isolated rat hearts. Biochem Biophys Res Comm 1991; 174 (2): 952–957.

    Article  PubMed  CAS  Google Scholar 

  59. Hilal-Dandan R, Urasawa K, Brunton LL. Endothelin inhibits adenylate cyclase and stimulates phosphoinositide hydrolysis in adult cardiac myocytes. J Biol Chem 1992; 267(15)10620–10624.

    Google Scholar 

  60. Lee CH, Parks D, Wu D et al. Members of the Gy a subunit gene family activate phospholipase C ß isozymes. J Biol Chem 1992; 267 (23): 16044–16047.

    PubMed  CAS  Google Scholar 

  61. Neer EJ. Heterotrimeric G proteins: organizers of transmembrane signals. Cell 1995; 80: 249–257.

    Article  PubMed  CAS  Google Scholar 

  62. Lamers JMJ, De Jonge HW, Panagia V et al. Receptor-mediated signalling pathways acting through hydrolysis of membrane phospholipids in cardiomyocytes. Cardioscience 1993; 4 (3): 121–131.

    PubMed  CAS  Google Scholar 

  63. Kentish J, Barsotti R, Lea T et al. Calcium release from cardiac sarcoplasmic reticulum induced by photorelease of calcium or Ins(1,4,5)P3. Am J Physiol 1990; 258: H610 - H615.

    PubMed  CAS  Google Scholar 

  64. Movsesian M, Thomas A, Selak M et al. Inositol triphosphate does not release Ca2+ from permeabilized cardiac myocytes and sarcoplasmic reticulum. FEBS Lett 1985; 185: 328–332.

    Article  PubMed  CAS  Google Scholar 

  65. Nosek TM, Williams MF, Zeigler ST et al. Inositol triposphate enhances calcium release in skinned cardiac and skeletal muscle. Am J Physiol 1986; 250: C807 - C811.

    PubMed  CAS  Google Scholar 

  66. Yuan S, Sunahara FA, Sen AK. Tumor-promoting phorbol esters inhibit cardiac functions and induce redistribution of protein kinase C in perfused beating rat hearts. Circ Res 1987; 61: 372–378.

    Article  PubMed  CAS  Google Scholar 

  67. Capogrossi MC, Kaku T, Filburn CR et al. Phorbol ester and dioctanoylglycerol stimulate membrane association of protein kinase C and have a negative inotropic effect mediated by changes in cytosolic Cat+ in adult rat cardiac myocytes. Circ Res 1990; 666x143–1155.

    Google Scholar 

  68. MacLeod KT, Harding SE. Effects of phorbol ester on contraction, intracellular pH and intracellular Ca2+ in isolated mammalian ventricular myocytes. J Physiol (Lond) 1991; 444481–498.

    Google Scholar 

  69. Pi Y, Sreekumar R, Huang X et al. Positive inotropy mediated by diacylglycerol in rat ventricular myocytes. Circ Res 1997; 81(1):92-loo.

    Google Scholar 

  70. Washizuka T, Hone M, Watanuki M et al. Endothelin-1 inhibits the slow component of cardiac delayed rectifier K+ currents via a pertussis toxin-sensitive mechanism. Circ Res 1997; 81 (2): 2u - 218.

    Article  Google Scholar 

  71. Ono K, Tsujimoto G, Sakamoto A et al. Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents. Nature 1994; 370: 301–304.

    Article  PubMed  CAS  Google Scholar 

  72. Kim D. Endothelin activation of an inwardly rectifying K+ current in atrial cells. Circ Res 1991; 69 (1): 25o - 255.

    Article  Google Scholar 

  73. James AF, Xie L, Fujitani Y et al. Inhibition of the cardiac protein kinase A-dependent chloride conductance by endothelin-i. Nature 1994; 370: 297–300.

    Article  PubMed  CAS  Google Scholar 

  74. Habuchi Y, Tanaka H, Furukawa T et al. Endothelin enhances delayed potassium current via phospholipase C in guinea pig ventricular myocytes. Am J Physiol 1992; 262: H345 - H354.

    PubMed  CAS  Google Scholar 

  75. Venema RC, Raynor RL, Noland Jr TA et al. Role of protein kinase C in the phosphorylation of cardiac myosin light chain 2. Biochem J 1993; 294: 401–406.

    PubMed  CAS  Google Scholar 

  76. Noland Jr TA, Kuo JF. Protein kinase C phosphorylation of cardiac troponin I and troponin T inhibits Cat+-stimulated MgATPase activity in reconstituted actomyosin and isolated myofibrils, and decreases actin-myosin interactions. J Mol Cell Cardiol 1993; 25: 53–65.

    Article  PubMed  CAS  Google Scholar 

  77. Damron DS, Van Wagoner DR, Moravec CS et al. Arachidonic acid and endothelin potentiate Cal+ transients in rat cardiac myocytes via inhibition of distinct K+ channels. J Biol Chem 1993; 268(36)27335–27344.

    Google Scholar 

  78. Meyer-Lehnert H, Wanning C, Predel H et al. Effects of endothelin on sodium transport mechanisms: potential role in cellular Ca2+ mobilization. Biochem Biophys Res Commun 2989; 163: 45 8–465.

    Google Scholar 

  79. Pucéat M, Clément-Chomienne O, Terzic A et al. a,-Adrenoceptor and purinoceptor agonists modulate Na-H antiport in single cardiac cells. Am J Physiol 1993; 264:H3io-H319.

    Google Scholar 

  80. Aharonovitz O, Granot Y. Stimulation of mitogen-activated protein kinase and Na+/H+ exchanger in human platelets. Differential effect of phorbol ester and vasopressin. J Biol Chem 1996; 271 (28): 16494–16499.

    Article  PubMed  CAS  Google Scholar 

  81. Pucéat M, Hilal-Dandan R, Strulovici B et al. Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes. J Biol Chem 1994; 269 (24): 16938–16944.

    PubMed  Google Scholar 

  82. Bogoyevitch MA, Glennon PE, Anderson MB et al. Endothelin-i and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem 1993; 1110–1119.

    Google Scholar 

  83. Disatnik M, Buraggi G, Mochly-Rosen D. Localization of protein kinase C isozymes in cardiac myocytes. Exp Cell Res 1994; 210: 287–297.

    Article  PubMed  CAS  Google Scholar 

  84. Johnson JA, Gray MO, Chen C et al. A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J Biol Chem 1996; 271 (4o): 24962–24966.

    Article  PubMed  CAS  Google Scholar 

  85. Venema RC, Kuo JF. Protein kinase C-mediated phosphorylation of troponin I and C-protein in isolated myocardial cells is associated with inhibition of myofibrillar actomyosin MgATPase. J Biol Chem 1993; 268 (4): 2705–2711.

    PubMed  CAS  Google Scholar 

  86. Morano I, Hofmann F, Zimmer M et al. The influence of P-light chain phosphorylation by myosin light chain kinase on the calcium sensitivity of chemically skinned heart fibres. FEBS Lett 1985; 189 (2): 221–224.

    Article  PubMed  CAS  Google Scholar 

  87. Sweeney HL, Stull JT. Phosphorylation of myosin in permeabilized mammalian cardiac and skeletal muscle cells. Am J Physiol 1986; 250: C657 - C66o.

    PubMed  CAS  Google Scholar 

  88. Jideama NM, Noland Jr TA, Raynor RL et al. Phosphorylation specificities of protein kinase C isozymes for bovine cardiac troponin I and troponin T and sites within these proteins and regulation of myofilament properties. J Biol Chem 1996; 271 (38): 23277–23283.

    Article  PubMed  CAS  Google Scholar 

  89. Reid JJ, Wong-Dusting HK, Rand MJ. The effect of endothelin on noradrenergic transmission in rat and guinea-pig atria. Eur J Pharmol 1989; 168: 93–96.

    Article  CAS  Google Scholar 

  90. Vogelsang M, Broede-Sitz A, Schäfer E et al. Endothelin ETA-receptors couple to inositol phosphate formation and inhibition of adenylate cyclase in human right atrium. J Cardiovasc Pharmacol 1994; 23: 344–347.

    Article  PubMed  CAS  Google Scholar 

  91. Van Biesen T, Muttrell LM, Hawes BE et al. Mitogenic signaling via G protein-coupled receptors. Endocr Rev 1996; 17 (6): 698–714.

    PubMed  Google Scholar 

  92. Ye H, Wolf RA, Kurz T et al. Phosphatidic acid increases in response to noradrenaline and endothelin-1 in adult rabbit ventricular myocytes. Cardiovasc Res 1994; 28: 1828–1834.

    Article  PubMed  CAS  Google Scholar 

  93. Lindmar R, Löffelhotz K. Phospholipase D in heart: basal activity and stimulation by phorbol esters and aluminum fluoride. Arch Pharmacol 1992; 346607–613.

    Google Scholar 

  94. Sadoshima J, Qiu Z, Morgan JP et al. Angiotensin II and other hypertrophic stimuli mediated by G protein-coupled receptors activate tyrosine kinase, mitogen-activated protein kinase, and 90-kD S6 kinase in cardiac myocytes. The critical role of Cat+-dependent signaling. Circ Res 1995; 76 (1): 1–15.

    Article  PubMed  CAS  Google Scholar 

  95. Sugden PH, Bogoyevitch MA. Intracellular signalling through protein kinases in the heart. Cardiovasc Res 1995; 30: 478–492.

    PubMed  CAS  Google Scholar 

  96. Bogoyevitch MA, Glennon PE, Sugden PH. Endothelin-i, phorbol esters and phenylephrine stimulate MAP kinase activities in ventricular cardiomyocytes. FEBS Lett 1993; 317(3)271–275.

    Google Scholar 

  97. Lazou A, Bogoyevitch MA, Clerk A et al. Regulation of mitogen-activated protein kinase cascade in adult rat heart preparations in vitro. Circ Res 1994; 75 (5): 932–941.

    Article  PubMed  CAS  Google Scholar 

  98. Lembo G, Hunter JJ and Chien KR. Signaling pathways for cardiac growth and hypertrophy. Recent advances and prospects for growth factor therapy. Ann N Y Acad Sci 1995; 752: 115–127.

    Article  PubMed  CAS  Google Scholar 

  99. Shubeita HE, McDonough PM, Harris AN et al. Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. J Biol Chem 1990; 265(33)20555–20562.

    Google Scholar 

  100. Bogoyevitch MA, Marshall CJ, Sugden PH. Hypertrophic angonists stimulate the activities of the protein kinase c-Raf and A-Raf in cultured ventricular myocytes. J Biol Chem 1995; 270 (44): 26303–26310.

    Article  PubMed  CAS  Google Scholar 

  101. Gardner AM, Vaillancourt RR, Johnson GL. Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase by G protein and tyrosine kinase oncoproteins. J Biol Chem 1993; 268: 17896–17901.

    PubMed  CAS  Google Scholar 

  102. Winitz S, Russell M, Qian N et al. Involvement of Ras and Raf in the Gi-coupled acetylcholine muscarinic m2 receptor activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. J Biol Chem 1993; 268: 19196–19199.

    PubMed  CAS  Google Scholar 

  103. Kiss Z. Regulation of phospholipase D by protein kinase C. Chem Phys Lipids 1996; 80: 81–102.

    Article  PubMed  CAS  Google Scholar 

  104. Exton JH. New developments in phospholipase D. J Biol Chem 1997; 272(25)15579–15582.

    Google Scholar 

  105. Friedlaender MM, Jain D, Ahmed Z et al. Endothelin activation of phospholipase D: dual modulation by protein kinase C and Ca2+. Am J Physiol 1993; 264: F845 - F853.

    PubMed  CAS  Google Scholar 

  106. Billah MM, Eckel S, Mullmann TJ et al. Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. J Biol Chem 1989; 264: 17069–17077.

    PubMed  CAS  Google Scholar 

  107. Baldi E, Musial A, Kester M. Endothelin stimulates phosphatidylcholine hydrolysis through both PLC and PLD pathways in mesangial cells. Am J Physiol 1994; 266: F957 - F965.

    PubMed  CAS  Google Scholar 

  108. Rybin VO, Steinberg SF. Protein kinase C isoform expression and regulation in the developing rat heart. 1994; 74 (2): 299–309.

    CAS  Google Scholar 

  109. Brown HA, Gutowski S, Moomaw CR et al. ADP-ribosylation factor, a small GTPdependent regulatory protein, stimulates phospholipase D activity. Cell 1993; 75x137–1144.

    Google Scholar 

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  1. Meredith Bond
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Editors and Affiliations

  1. Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA

    David M. Pollock Ph.D.

  2. Department Molecular and Cellular Physiology, University of Cincinnati Medical Center Cincinnati, Ohio, USA

    Robert F. Highsmith Ph.D.

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Bond, M. (1998). Endothelin Regulation of Cardiac Contractility: Signal Transduction Pathways. In: Pollock, D.M., Highsmith, R.F. (eds) Endothelin Receptors and Signaling Mechanisms. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-11672-2_11

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  • DOI: https://doi.org/10.1007/978-3-662-11672-2_11

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