Evidence for a histamine H2 receptor that inhibits pepsin secretion in the dog.
H+ and pepsin output were studied in four gastric fistula dogs with histamine and in five dogs with 4-methylhistamine (4(Me)H), an H2 histamine receptor agonist with little H1 effect. Each amine was given in 45-min incremental step doses to constitute full dose-response curves. Pepsin output was biphasic with both drugs. Peak pepsin output occurred at low doses (less than or equal to 5 microgram/kg-h) and progressive inhibition of output was seen at higher doses, but H+ output was stimulated at all doses. The H2 receptor antagonist, cimetidine, competitively inhibited H+ stimulation. The pepsin response to histamine or 4(Me)H was converted to a positive logsigmoid response when cimetidine was given at the same time. In the presence of cimetidine (1 mg/kg-h), the outputs of H+ and pepsin were positively correlated in the full histamine dose range. These data show that histamine effects on pepsin secretin are a mixture of stimulation and inhibition and that the receptor responsible for pepsin stimulation is of a high affinity, low Km, H2 type, whereas inhibition at high doses of histamine is probably mediated by a low affinity, high Km receptor, also H2 type.
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005747:Gastric Fistula; D005750:Gastric Juice / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism*; D011968:Receptors, Histamine / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013270:Stomach / Q000502:physiology
D006146:Guanidines; D008761:Methylhistamines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D010434:Pepsin A