Effect of H2-receptor antagonists on rat liver cytosolic acetyl CoA:arylamine N-acetyltransferase activity.
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.
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202.
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Svensson
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Tomilo
D000120:Acecainide / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D015738:Famotidine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006635:Histamine H2 Antagonists; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine; D000120:Acecainide; D001191:Arylamine N-Acetyltransferase