Ontogenic differences in the functions of myocardial alpha1 adrenoceptor subtypes in rats.
The present study was done to determine possible ontogenic differences in the functions of rat myocardial alpha1, adrenoceptor (alpha1 AR) subtypes in view of reported greater inotropic responses of myocardium of neonatal than of adult rats to alpha1, AR agonists. Methoxamine, phenylephrine and norepinephrine were used as alpha1 AR agonists. Phenylephrine and norepinephrine were used in the presence of 3 microM propranolol. It was found that the ratios of chloroethylclonidine (CEC)-insensitive alpha1 AR subtype (alpha1A AR) to CES-sensitive alpha, AR subtype (alpha1B AR) were approximately 50:50 in neonatal (1 week old) and 20:80 in adult rat ventricles. alpha1A AR selective antagonists WB 4101 and 5-methylurapidil+ (5-MU) inhibited the inotropic effects of alpha1, AR agonists both on neonatal and on adult rat ventricles; in contrast, selective inactivation of alpha1B AR by CEC inhibited the inotropic effects of alpha1 AR agonists only on ventricles from adult but not from neonatal animals. WB 4101 inhibited methoxamine-induced increases in inositol phosphates by ventricular slices from both adult and neonatal rats; in contrast, CEC inhibited these effects of methoxamine only in tissues from adult but not in tissues from neonatal animals. In conclusion, this study, to our knowledge, demonstrates for the first time that the effects of alpha AR agonists on right ventricular contractions and phosphoinositol turnover are mediated primarily by alpha 1A AR subtype in the neonatal and by both alpha1A AR and alpha1B AR subtypes in the adult rat.
Deng
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Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Chemtob
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Almazan
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Varma
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D008729:Methoxamine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D008729:Methoxamine; D009638:Norepinephrine; D011224:Prazosin