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 [H-3]prazosin binding, and noradrenaline-stimulated [H-3]inositol phosphate production. Repopulation of alpha(1)-adrenoceptors was monoexponential, with a t(1/2) of 33 h; functional recovery was also monoexponential, with t(1/2) 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 [H-3]prazosin binding sites and the ability of a,-adrenoceptors to respond to noradrenaline. Moreover, based on competition curves for inhibition of specific [H-3]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.