CHARACTERIZATION OF THE HUMAN LIVER ALPHA(1)-ADRENOCEPTORS - PREDOMINANCE OF THE ALPHA(1A) SUBTYPE

The alpha(1)-adrenoceptor subtype present in human liver membranes was studied using radioligand binding techniques. [H-3]Prazosin binding w as rapid, saturable and reversible. A kinetically derived K-d of 0.22 nM was obtained. Rosenthal analysis of saturation isotherms indicated a single class of binding sites with a K-d of 0.47 nM and a B-max of 7 0 fmol/mg of protein. Membrane preincubation with chloroethylclonidine markedly decreased total binding (62% decrease) without altering the K-d for the radioligand. Binding competition experiments were performe d and the order of potency for agonists was: oxymetazoline > epinephri ne greater than or equal to norepinephrine > methoxamine. The binding affinity for epinephrine was modulated by the GTP analogue guanosine-5 '-(beta,gamma-imido)triphosphate. For antagonists the potency order wa s: WB4101 greater than or equal to prazosin greater than or equal to ( +)-niguldipine = 5-methylurapidil greater than or equal to benoxathian greater than or equal to phentolamine. The pharmacological profile of the [H-3]prazosin binding sites of human liver membranes suggests tha t alpha(1A)-adrenoceptors predominate (75%-85% of the alpha(1)-adrenoc eptors) in this tissue.