Neurochemical Research

, Volume 21, Issue 2, pp 217–229 | Cite as

Cardiac α1-Adrenoceptors that regulate contractile function: Subtypes and subcellular signal transduction mechanismsthat regulate contractile function: Subtypes and subcellular signal transduction mechanisms

  • Masao Endoh
Original Articles


Activation of α1-adrenoceptors as well as endothelin (ET) and angiotensin II (Ang II) receptors in cardiac muscle is coupled to acceleration of the hydrolysis of phosphoinositide (PI), with resultant production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. There is an excellent correlation between the extent of acceleration of the PI hydrolysis and the positive inotropic effect (PIE) under most experimental conditions after the administration of α-adrenoceptor agonists, ET and Ang II in the rabbit ventricular muscle. The PIE of the α-adrenoceptor agonists, ET and Ang II is associated with a negative lusitropic effect and an increase in the sensitivity of myofilaments to Ca2+ ions. The PIE can be selectively inhibited by inhibitors of protein kinase C (PKC) such as staurosporine, NA 0345 and H-7, with little effect on the PI hydrolysis and the PIE of isoproterenol and Bay k 8644. Surprisingly, an activator of PKC, phorbol 12,13-dibutyrate (PDBu), selectively and more completely inhibited the PIE and acceleration of PI hydrolysis induced by the α-adrenoceptor agonists as well as by ET and Ang II in the rabbit. These receptor agonists consistently cause intracellular alkalinization by activation of Na+−H+ exchange, while the effects on membrane ion channel activities are divergent. For example, α-adrenoceptor agonists cause monophasic prolongation of the action potential, the time course of which coincides well with that of the PIE, while ET and Ang II produce a biphasic change in action potential duration, i.e., the long-lasting prolongation preceded by a transient abbreviation. α-Adrenoceptor agonists scarcely affect ICa, whereas ET elicits a biphasic alteration of the current. In addition, the potassium current, IKl, is markedly suppressed by α-adrenoceptor agonists, but this effect is not revealed with Ang II under the same experimental condition. These results indicate that the effects of α1-adrenoceptors stimulation are partially shared by those of ET and Ang II receptor activation in the heart. Approximately 60% of the total population of α1-adrenoceptors in the rabbit ventricle are composed of α1B subtype, which is susceptible to chlorethylclonidine (CEC) and is predominantly responsible for the α1-mediated PIE and PI hydrolysis. The remaining fraction that belongs to α1A-adrenoceptors subtype is further subclassified into the WB 4101-sensitive (partly coupled to PI hydrolysis) and the niguldipinesensitive (PI hydrolysis-unrelated) subtypes.

Key words

Phenylephrine methoxamine α1A-receptors α1B-receptors endothelin angiotensin II Ca2+ sensitivity phosphoinositide hydrolysis positive inotropic effect 


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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Masao Endoh
    • 1
  1. 1.Department of PharmacologyYamagata University School of MedicineYamagataJapan

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