Nature of [3H]rilmenidine binding to membranes of rat cerebral cortex.
The binding of [3H]rilmenidine to membranes of rat cerebral cortex was studied in order to ascertain which receptor populations this novel antihypertensive interacts with in the cortex. A catecholamine-sensitive, alpha 2-adrenoceptor binding site was identified which represented up to 50% of specific, 2 nmol/L [3H]rilmenidine binding and was displaceable by the catecholamines in the rank order epinephrine----norepinephrine----dopamine----isoproterenol. Some imidazolines such as clonidine, naphazoline, and idazoxan and the guanidino compound guanabenz completely and potently inhibited [3H]rilmenidine binding from both catecholamine-sensitive and -insensitive sites. The substituted imidazole and guanidine, cimetidine, and amiloride, respectively, showed no affinity for [3H]rilmenidine binding. The pharmacologic profile of the catecholamine-insensitive [3H]rilmenidine site in rat cerebral cortex suggests it may be novel, as it has the features of an imidazoline-guanidino-oxazoline binding site. However, its identity requires further characterization.
King
P R
PR
Clinical Pharmacology and Therapeutics Unit, University of Melbourne, Australia.
Gundlach
A L
AL
Jarrott
B
B
Louis
W J
WJ
D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002395:Catecholamines / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D010080:Oxazoles / Q000378:metabolism* / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D000077769:Rilmenidine; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D006146:Guanidines; D007093:Imidazoles; D010080:Oxazoles; D011941:Receptors, Adrenergic; D014316:Tritium; D015016:Yohimbine; D000584:Amiloride; D019791:Guanidine; D000077769:Rilmenidine; D011224:Prazosin