Cholinergic mechanism of acid secretion in the dog: an in vivo and in vitro comparison.
The effect of cholinergic stimulation on gastric acid secretion was examined in mongrel dogs using an in vivo and an in vitro preparation for comparison. The gastric fistula dog was used for the in vivo studies, and methacholine was infused directly into the artery supplying the fundus of the stomach to avoid systemic hemodynamic changes. Isolated parietal cells were used for the in vitro studies. In vivo, methacholine infused at 1 microgram/min was found to stimulate gastric acid secretion that was inhibited 98.5 +/- 1.4% by intravenously administered metiamide (H2 blocker) and 72 +/- 11% by intra-arterially administered glucagon. Glucagon had no effect on histamine stimulated acid secretion. In vitro, increasing concentrations of methacholine from 10(-7), 10(-6) to 10(-5) M stimulated [14C]aminopyrine uptake into parietal cells in a concentration dependent manner. This effect of methacholine was unaltered by 10(-4) M metiamide or 10(-6) M glucagon. However, atropine 10(-5) M totally blocked the stimulatory effect of methacholine. Our data suggest that the cholinergic mechanism of acid secretion is different when examined in vivo vs. in vitro even in the same species. In vivo histamine dependency has a major contribution to the cholinergic mechanism of acid secretion, whereas in vitro the interaction of the cholinergic agonist at the muscarinic receptor results in acid stimulation that does not require the presence of histamine.
D000632:Aminopyrine / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005748:Gastric Fundus / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000294:innervation*; D005934:Glucagon / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D008785:Metiamide / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects
D008688:Methacholine Compounds; D010277:Parasympathomimetics; D000632:Aminopyrine; D008785:Metiamide; D001285:Atropine; D006632:Histamine; D005934:Glucagon