Molecular Pharmacology, Vol 20, 240-243, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Solubilization of a [³H]Cimetidine Binding Site from Rat Brain

A Clonidine-Sensitive H-2 Receptor Subtype?

¹ Department of Pharmacology, Duke University Medical Center, Durham North Carolina 27710

A binding site for [³H]cimetidine was obtained from rat brain membranes solubilized with digitonin. The site displayed saturability, high affinity, and drug specificity for imidazole H-2 antagonists and was able to bind ligand at physiological temperatures. The regional distribution of binding sites paralleled that of neuronal histamine projections. Displacement of binding did not occur readily with H-2 agonists, and, although 2-guanidino-4-[2-(2-cyano-3-methyl-guanidino)ethyl-thiomethyl]thiazole (ICI 125,211, (a non-imidazole H-2 antagonist) displaced [³H]cimetidine, it was less potent than imidazole antagonists. Micromolar concentrations of clonidine, a substance thought to stimulate a central imidazole H-2 receptor subtype, were able to displace [³H]cimetidine binding, and chronic treatment of rats with clonidine in vivo resulted in down-regulation of the sites. These data suggest that the solubilized [³H]cimetidine binding site is associated with the putative clonidine-sensitive H-2 receptor subtype.