Trist D G, Leff P, Black J, Gerskowitch V P, Shankley N P
Wellcome Research Laboratories, Beckenham Kent, U.K.
J Pharmacol Exp Ther. 1987 Dec;243(3):1043-7.
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.
西咪替丁被广泛用作外周和中枢组织中组胺H2受体分类的配体。在离体组织试验和脑腺苷酸环化酶试验中，它表现出明显简单的竞争性拮抗作用。在本研究中，将其在心脏腺苷酸环化酶试验中的作用与其在离体豚鼠右心房制备中的作用进行了比较。使用组胺或英普咪定，西咪替丁在完整组织试验中表现出相似的亲和力（pKB = 6.1）。在豚鼠心室的洗涤匀浆中，西咪替丁似乎竞争性拮抗组胺对腺苷酸环化酶的刺激，但估计的pKB为6.7。相比之下，替丁在两种试验中的pKB相似（7.7）。应用最近开发的浓度比方法表明，西咪替丁在环化酶试验中表现出一种综合作用，包括竞争性H2受体拮抗作用和涉及受体后作用的额外抑制特性。浓度比分析使西咪替丁作用的纯竞争性成分在环化酶试验中得以量化，得出pKB为6.0。
