The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog.
We have previously demonstrated that both pentagastrin and methacholine can stimulate histamine release from the canine stomach during short term administration of the secretagogues into the gastrosplenic artery. In this study we tested the hypothesis that gastric histamine release determines the acid secretory response to acid secretagogues. Increasing doses of pentagastrin (2, 6, and 20 ng/kg/min) and methacholine (0.1, 0.3, and 1 micrograms/min) were infused into the gastrosplenic artery in dogs, while gastric acid output, histamine and N tau-methyl histamine secretory rates were monitored. Histamine and N tau-methyl histamine concentrations in plasma were measured using GC/NICI-MS. Increasing doses of pentagastrin resulted in increasing gastric output. Total histamine secretory rate expressed as the sum of histamine and N tau-methyl histamine secretory rate showed a significant increase above basal with the two highest doses of pentagastrin. Regression analysis correlating the dose of pentagastrin to gastric acid output gave a correlation coefficient of 0.586 which was very significant. Regression analysis correlating the total histamine secretory rate to acid output gave a correlation coefficient of 0.498 which was also very significant. Increasing doses of methacholine also resulted in a dose-dependent increase in acid output. Histamine secretory rates showed a statistically significant increase above basal only at the 1 microgram/min infusion rate, however, the total histamine secretory rates (histamine + N tau-methyl histamine) were no longer significant at any of the doses of methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)
Gerber
J G
JG
Division of Clinical Pharmacology and Toxicology (C-237), University of Colorado Health Sciences, Denver 80262, USA.
Payne
N A
NA
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism*; D006632:Histamine / Q000097:blood; D006636:Histamine Release / Q000502:physiology*; D007261:Infusions, Intra-Arterial; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008761:Methylhistamines / Q000097:blood; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects
D008761:Methylhistamines; D018721:Muscarinic Agonists; D016210:Methacholine Chloride; C031205:3-methylhistamine; D006632:Histamine; D010418:Pentagastrin