Characterization of the alpha 1A-adrenoceptors of guinea pig liver membranes: studies using 5-[3H]methylurapidil.
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.
García-Sáinz
J A
JA
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City.
Romero-Avila
M T
MT
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010879:Piperazines; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects / Q000378:metabolism*
D000477:Alkylating Agents; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; C057446:5-methylurapidil; C051731:chlorethylclonidine; D003000:Clonidine