Phenoxybenzamine partially inhibits alpha 2-adrenoceptors without affecting their presynaptic function.

The turnover of alpha-adrenoceptors was assessed by administering phenoxybenzamine (PBZ) intraperitoneally to rats in order to block the receptors irreversibly. The reappearance of the binding of [3H]prazosin, [3H]clonidine and [3H]rauwolscine in membranes from cerebral cortices was then measured. Maximum inhibition of binding occurred 3 hr after administration of phenoxybenzamine. The binding of [3H]prazosin was inhibited by 95% after administration of phenoxybenzamine (2 X 4 mg/kg, i.p.), and the half life (t1/2) for the alpha 1-adrenoceptor was 1.87 days. The "turnover" of binding for the alpha 2-adrenoceptor ligands ([3H]clonidine and [3H]rauwolscine) was similar: with doses of phenoxybenzamine up to 15 mg/kg (i.p.), the binding of both ligands was inhibited to a maximum of 30%. Maximum recovery occurred 3 days after treatment with phenoxybenzamine and the alpha 2-adrenoceptor has an apparent half life for recovery of 12 hr. Since only partial blockade of alpha 2-adrenoceptors was possible with phenoxybenzamine the possibility that these blocked sites included functional presynaptic autoreceptors was investigated. Clonidine (1 microM) attenuated K+-induced release of preloaded [3H]noradrenaline from cortical synaptosomes prepared from control rats by some 35%. Clonidine inhibited this release of [3H]noradrenaline to the same extent in synaptosomes prepared from rats treated with phenoxybenzamine 3 hr prior to sacrifice. This indicates that the alpha 2-adrenoceptors which are blocked by phenoxybenzamine are not part of the functional receptor population.