Solubilization of a [3H]cimetidine binding site from rat brains. a clonidine-sensitive H-2 receptor subtype?
Subramanian, N.; Slotkin, T.A.
Molecular Pharmacology 20(2): 240-243
1981
ISSN/ISBN: 0026-895X PMID: 6272082 Document Number: 168640
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-methylguanidino)ethylthiomethyl]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. Apparently the solubilized [3H]cimetidine binding site is associated with the putative clonidine-sensitive H-2 receptor subtype.