In vivo recovery of alpha 1-adrenoceptors in rat myocardial tissue after alkylation with phenoxybenzamine.
The rate of recovery of rat myocardial alpha 1-adrenoceptor density and responsiveness after in vivo block with phenoxybenzamine (1 mg/kg, i.p.) have been investigated by measuring [3H]prazosin binding, and noradrenaline-stimulated [3H]inositol phosphate production. Repopulation of alpha 1-adrenoceptors was monoexponential, with a t1/2 of 33 h; functional recovery was also monoexponential, with t1/2 of 28 h. Furthermore, our results clearly demonstrate the absence of a receptor reserve for alpha 1-adrenoceptors mediating noradrenaline-stimulated phosphoinositide breakdown in rat myocardial tissue. These observations indicate a close relationship between the density of [3H]prazosin binding sites and the ability of alpha 1-adrenoceptors to respond to noradrenaline. Moreover, based on competition curves for inhibition of specific [3H]prazosin by WB-4101 to rat myocardial membranes 48 h and 7 days after the administration of phenoxybenzamine, the results suggest that rat myocardial membranes contain both alpha 1-adrenoceptors subtypes, i.e., alpha 1A and alpha 1B, in an approximate ratio of 20:80, and this relative ratio does not seem to be altered during the recovery process.
Sallés
J
J
Departament de Farmacologia i Psiquiatria, Facultat de Medicina, Universitat Autònoma de Barcelona, Spain.
Gascón
S
S
Ivorra
D
D
Badia
A
A
D000478:Alkylation; D000818:Animals; D001665:Binding Sites; D006321:Heart / Q000187:drug effects; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D009638:Norepinephrine; D011224:Prazosin