Histamine H-2 receptor stimulation and inhibition of pepsin secretion in the dog.

Abstract

Although low doses of histamine (less than 150 nM/kg.hr) stimulate pepsin secretion, higher doses inhibit pepsin secretion in a dose-dependent manner. To better histamine stimulation of pepsin, histamine was used at doses at the lower end of the dose-response scale in five dogs with gastric fistula. Five doses of histamine below the ED50 for acid, viz, 9, 22.5, 67.5, 90 and 112 nM/kg.hr in 45-min steps, provided values for pepsin secretion from which Ed50 = 11.4 nmol/kg.hr (i.e., about 1/12 the ED50 for acid) and calculated maximum 22,600 peptic U/30 min were calculated. To document the inhibition, pepsin secretion was first stimulated by an infusion of bethanechol (0.4 mumol/kg.hr). A super-added injection of the histamine H-2 agonist 4-methylhistamine (0.4 or 0.8 mumol/kg) produced strong additional acid stimulation and immediate 40% suppression of pepsin secretion. The ratio pepsin/acid was reduced to one-third of control for the 90 min after 4-methylhistamine. The most specific H-2 agonist impromidine had the same effects, whereas pentagastrin (1.95 nmol/kg) inhibited both acid and pepsin secretion stimulated by bethanechol. The specificity of H-2 effect of impromidine was confirmed by simultaneous tachycardia and hypotension; pentagastrin did not produce cardiovascular effects. These studies confirm the unique effect of histamine on the peptic cell of the dog in which both stimulation and inhibition are H-2 receptor-mediated effects.

• Authors: B I Hirschowitz, J Rentz, E Molina
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 218 Issue 3 Pg. 676-80 (Sep 1981) ISSN: 0022-3565 [Print] United States
• PMID: 6455514 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Guanidines
• Imidazoles
• Methylhistamines
• Receptors, Histamine
• Receptors, Histamine H2
• 4-methylhistamine
• Histamine
• Impromidine
• Pepsin A

Topics

• Animals
• Dogs
• Gastric Juice (metabolism)
• Gastric Mucosa (drug effects, metabolism)
• Guanidines (pharmacology)
• Histamine (pharmacology)
• Imidazoles (pharmacology)
• Impromidine
• Methylhistamines (pharmacology)
• Pepsin A (metabolism)
• Receptors, Histamine (drug effects)
• Receptors, Histamine H2 (drug effects)