Elsevier

Brain Research

Volume 344, Issue 1, 30 September 1985, Pages 89-95
Brain Research

The effects of phenoxybenzamine on specific binding and function of central α-adrenoceptors in the rabbit

https://doi.org/10.1016/0006-8993(85)91191-6Get rights and content

Abstract

We have studied the effects of phenoxybenzamine, an irreversible α-adrenoceptor antagonist on the binding of the α-adrenoceptor ligands [3H]prazosin and [3H]clonidine to rabbit brain membranes. Where possible changes in binding were related to changes in central α-adrenoceptor function. Phenoxybenzamine showed a similar α12-adrenoceptor selectivity in the brain to that previously reported in the periphery. Much higher doses were required to reduce specific clonidine binding and to interfere with the hypotensive response to intracisternal clonidine than to reduce specific prazosin binding. Recovery of binding site number of both α1- and α2-adrenoceptor selective ligands was slower than in peripheral tissues (heart and spleen). Recovery was log linear and the half time (t1/2) for recovery of the maximum number of specific prazosin and clonidine binding sites in forebrain was 10.8 ± 2.6days and 6.1 ± 0.1days and in hindbrain 13.3 ± 3.1days and 4.6 ± 1.8days, respectively.t1/2 for recovery of the in vivo hypotensive response to intracisternal clonidine was 2.7 ± 1.0days. Recovery of this response was attenuated by treatment with the inhibitor of protein synthesis, 5-fluorouracil. This suggests that recovery after phenoxybenzamine in brain, as in the periphery, may depend at least in part on synthesis of new receptor protein. The recovery of brain adrenoceptor number after phenoxybenzamine may be an index of receptor turnover and is much slower in brain than in heart and spleen.

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