Binding of the imidazoline UK-14, 304, a putative full alpha 2-adrenoceptor agonist, to rat cerebral cortex membranes.
The aryl imidazoline compound UK-14, 304 (5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline) is a potent and selective alpha 2-adrenoceptor agonist with full intrinsic activity, unlike other imidazolines. We examined the characteristics of high specific activity (84 Ci/mmol) [3H]UK-14, 304 binding to rat cerebral cortex membranes. [3H]UK-14, 304 specific binding was enhanced by Mn2+ ion, and associated and dissociated moderately rapidly at 25 degrees C. Norepinephrine-displaceable binding was saturable and monophasic, with a KD of 1.4 nM, in agreement with rate and competition experiments, and a Bmax of 200 fmol/mg protein. Competition studies revealed that binding was alpha 2-adrenoceptor-specific, with yohimbine being 12 times more potent than prazosin. [3H]UK-14, 304 appeared to label predominantly the R(H) state of the brain alpha 2-adrenoceptor, as judged by the high affinity of catecholamine and imidazoline agonists (IC50, 1-13 nM), and the relatively low affinity of yohimbine and rauwolscine (IC50, 100-300 nM), at the binding site. [3H]UK-14, 304 compares favorably with other alpha 2-adrenoceptor ligands because of its high affinity and specific activity.
D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D000068438:Brimonidine Tartrate; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011810:Quinoxalines / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate