Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine

M Taouis, M Berlan and M Lafontan

The recovery of post- and extrasynaptic alpha 2-adrenergic receptor- binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with [3H]yohimbine, whereas [3H]clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, [3H] clonidine and [3H]yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2-binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2-agonists) in fat cells inasmuch as occupancy of 15% of [3H]clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations using the approach described in the present paper.

Volume 31, Issue 1, pp. 89-96, 01/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				J. Bodenstein, D. P. Venter, and C. B. Brink Phenoxybenzamine and Benextramine, but Not 4-Diphenylacetoxy-N-[2-chloroethyl]piperidine Hydrochloride, Display Irreversible Noncompetitive Antagonism at G Protein-Coupled Receptors J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 891 - 905. [Abstract] [Full Text] [PDF]

				C. B. Brink, S. M. Wade, and R. R. Neubig Agonist-Directed Trafficking of Porcine alpha 2A-Adrenergic Receptor Signaling in Chinese Hamster Ovary Cells: l-Isoproterenol Selectively Activates Gs J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 539 - 547. [Abstract] [Full Text]