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

Abstract : 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.
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https://hal-cnrs.archives-ouvertes.fr/hal-03525720
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Submitted on : Friday, January 14, 2022 - 8:54:10 AM
Last modification on : Monday, July 4, 2022 - 9:49:23 AM

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  • HAL Id : hal-03525720, version 1
  • PUBMED : 2880286

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Mohammed Taouis, M Berlan, M Lafontan. Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine.. Molecular Pharmacology, 1987, 31 (1), pp.89-96. ⟨hal-03525720⟩

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