Differential Inotropic Effects of Endothelin-1, Angiotensin II, and Phenylephrine Induced by Crosstalk With cAMP-Mediated Signaling Process in Dog Ventricular Myocardium

Journal of Pharmacological Sciences

Ikuo Norota¹  Li Chu¹  Masao Endoh¹  Kuniaki Ishii¹  Shin-ichi Yomogida¹ 

[1] Department of Cardiovascular Pharmacology, Yamagata University School of Medicine

关键词: inotropic effect;    Gq protein-coupled receptor;    cAMP;    Bay k 8644;    dog ventricular myocardium;   

DOI  :  10.1254/jphs.FP0040412

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(33)Cited-By(8)Endothelin-1 (ET-1), angiotensin II (Ang II), and phenylephrine, an α1-adrenoceptor agonist, share the common signaling process, resulting in activation of Gq protein-coupled receptor (GqPCR) to activate the hydrolysis of phosphoinositide (PI). They do not elicit any inotropic effect in isolated dog ventricular muscle. In the presence of forskolin or IBMX (3-isobutyl-1-methylxanthine), ET-1 produced a dual effect, that is, a positive inotropic effect (PIE) and/or a negative inotropic effect (NIE) depending on concentrations of forskolin or IBMX present simultaneously with ET-1. Phenylephrine produced a definite PIE and Ang II induced a small and transient PIE in the presence of forskolin or IBMX, but they did not elicit a NIE. Facilitation of Ca2+ influx via L-type Ca2+ channel may play a crucial role in the crosstalk because GqPCR agonists produced, likewise a PIE in the presence of Bay k 8644. GqPCR agonists failed to induce a PIE in the presence of dihydroouabain or elevated [Ca2+]o. These findings indicate that the accumulation of cAMP or activation of L-type Ca2+ channels markedly modulates the inotropic response to GqPCR agonists in a manner that leads to a PIE in dog ventricular myocardium. In addition, ET-1, but not Ang II or phenylephrine, activates the signal transduction process that results in a NIE.

【 授权许可】

Unknown