Characterization of the alpha 1A-adrenoceptors of guinea pig liver membranes: studies using 5-[3H]methylurapidil

JA Garcia-Sainz and MT Romero-Avila

Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico City.

Binding of 5-[3H]methylurapidil to guinea pig liver membranes was rapid, saturable, and reversible. Scatchard analysis of saturation isotherms indicated a single class of binding sites with a Kd of 0.86 nM and a Bmax of 36 fmol/mg of protein. Preincubation of the membranes with chlorethylclonidine did not alter significantly the binding parameters for 5-[3H]methylurapidil. Binding competition experiments were performed, and the order of potency for agonists was oxymetazoline > epinephrine > norepinephrine >> methoxamine; for antagonists, the potency order was (+)-niguldipine > or = 5-methylurapidil = prazosin = WB4101 > benoxathian > or = phentolamine > or = (-)-niguldipine. The binding affinity for epinephrine was modulated by the hydrolysis- resistant GTP analogue guanosine-5'-(beta, gamma-imido)triphosphate. The pharmacological profile of the 5-[3H]methylurapidil binding sites of guinea pig liver differs markedly from those of the cloned alpha 1- adrenoceptors (i.e., alpha 1B-, alpha 1C-, and alpha 1A/D- adrenoceptors) and resembles that of the classical alpha 1A receptor subtype.

Volume 44, Issue 3, pp. 589-594, 09/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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