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. [3H]Prazosin binding was rapid, saturable and reversible. A kinetically derived Kd of 0.22 nM was obtained. Rosenthal analysis of saturation isotherms indicated a single class of binding sites with a Kd of 0.47 nM and a Bmax of 70 fmol/mg of protein. Membrane preincubation with chloroethylclonidine markedly decreased total binding (62% decrease) without altering the Kd for the radioligand. Binding competition experiments were performed and the order of potency for agonists was: oxymetazoline > epinephrine > or = norepinephrine > methoxamine. The binding affinity for epinephrine was modulated by the GTP analogue guanosine-5'-(beta,gamma-imido)triphosphate. For antagonists the potency order was: WB4101 > or = prazosin > or = (+)-niguldipine = 5-methylurapidil > or = benoxathian > or = phentolamine. The pharmacological profile of the [3H]prazosin binding sites of human liver membranes suggests that alpha 1A-adrenoceptors predominate (75%-85% of the alpha 1-adrenoceptors) in this tissue.