TY - JOUR T1 - Effect of H2-receptor antagonists on rat liver cytosolic acetyl CoA:arylamine N-acetyltransferase activity. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 74 LP - 78 VL - 20 IS - 1 AU - C K Svensson AU - M Tomilo Y1 - 1992/01/01 UR - http://dmd.aspetjournals.org/content/20/1/74.abstract N2 - This investigation examined the effect of cimetidine, famotidine, and ranitidine on rat liver acetyl CoA:arylamine N-acetyltransferase (NAT) activity. Studies were conducted using procainamide and p-aminobenzoic acid as substrate probes for NAT isozymes II and I, respectively. At an inhibitor:substrate ratio of 2:1, ranitidine, cimetidine, and famotidine reduced NAT II activity by 9, 48, and 75%, respectively. At this same ratio, none of the H2-receptor antagonists significantly reduced NAT I activity. The inhibition of NAT II activity by cimetidine and famotidine was mixed in nature, with characteristics consistent with predominantly competitive inhibitors. Preincubation of NAT with acetyl CoA did not attenuate the inhibitory effects of famotidine, suggesting this agent does not associate with the sulfhydryl of the critical cysteine residue on NAT. These results indicate the ability of H2-receptor antagonists to inhibit NAT activity with some degree of specificity for the two isozymes and significant differences in inhibitory potency between the antagonists. ER -