Alpha 1D-adrenoceptors do not contribute to inotropic responses of neonatal rat myocardium.
This study investigated the role of alpha 1D-adrenoceptors (ARs) in the inotropic responses of neonatal (7-day-old) rat myocardium by using the relatively selective antagonist BMY 7378. The positive inotropic effects of phenylephrine on right ventricular strips of neonatal rats were not inhibited by BMY 7378 up to a concentration of 300 nM but potently antagonized by the alpha 1AAR antagonist 5-methylurapidil (5-MU) (pKB, 8.73 +/- 0.12; n = 6). BMY 7378 was approximately 1,000-fold less potent (pKi, 6.63 +/- 0.7; n = 5) in inhibiting the binding of [3H]prazosin to right ventricular membrane preparations of neonatal rats than was 5-MU (pKi, 9.04 +/- 0.54; n = 5). Neonatal rat cerebral cortex and adult rat aorta were used as additional controls. BMY 7378 was a weak inhibitor of [3H]prazosin binding to neonatal cortex (pKi, 6.8 +/- 0.04; n = 3) but highly potent in inhibiting the binding to adult rat aortic membrane preparations (pKi for high-affinity binding, 9.70 +/- 0.30; n = 4); BMY 7378 potently antagonized the effects of phenyleprine on adult rat aortic strips (pKB, 9.05 +/- 0.11; n = 5). It is concluded that alpha 1DARs do not play a significant role in alpha 1AR-mediated inotropic responses of neonatal rat myocardium.
Deng
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XF
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Varma
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DR
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016276:Ventricular Function
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; C057446:5-methylurapidil; D010656:Phenylephrine; C053428:BMY 7378; D011224:Prazosin