The rate of recovery of rat myocardial α1-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 α1-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 α1-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 α1-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 α1-adrenoceptors subtypes, i.e., α1A and α1B, in an approximate ratio of 20:80, and this relative ratio does not seem to be altered during the recovery process. © 1994.
|Journal||European Journal of Pharmacology: Molecular Pharmacology|
|Publication status||Published - 1 Jan 1994|
- Myocardium (rat)
- Phosphoinositide hydrolysis
- [ H]Prazosin binding 3
- α -Adrenoceptor 1