PT  - JOURNAL ARTICLE
AU  - Trist, D G
AU  - Leff, P
AU  - Black, J
AU  - Gerskowitch, V P
AU  - Shankley, N P
TI  - Resultant action of cimetidine in a cardiac adenylate cyclase assay: its elucidation by concentration-ratios analysis.
DP  - 1987 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1043--1047
VI  - 243
IP  - 3
4099  - http://jpet.aspetjournals.org/content/243/3/1043.short
4100  - http://jpet.aspetjournals.org/content/243/3/1043.full
SO  - J Pharmacol Exp Ther1987 Dec 01; 243
AB  - Cimetidine is widely used as a ligand for the classification of histamine H2-receptors in peripheral and central tissues. It demonstrates apparently simple competitive antagonism in isolated tissue assays and in brain adenylate cyclase assays. In this study its action in a cardiac adenylate cyclase assay was compared with its effects in the isolated guinea pig right atrial preparation. Using either histamine or impromidine, cimetidine expressed similar affinity (pKB = 6.1) in the intact tissue assay. In washed homogenates of guinea pig ventricle cimetidine appeared to antagonize competitively the stimulation by histamine of adenylate cyclase but the estimated pKB was 6.7. In contrast, the pKB for tiotidine was similar in both assays (7.7). Application of a recently developed concentration-ratios method indicated that cimetidine expressed a resultant action in the cyclase assay consisting of competitive H2-receptor antagonism and an additional inhibitory property involving a postreceptor action. The concentration-ratios analysis allowed the purely competitive component of cimetidine action to be quantified in the cyclase assay giving a pKB of 6.0.