Effects of vagotomy on urecholine-modified histamine dose responses in dogs

Abstract

Histamine step-dose responses, 2-100 mug/kg-h in 6 successive 45-min steps, were studied in nine dogs with gastric cannula. In three of the dogs the gastric fundus was selectively vagally denervated and the dose responses were repeated. In both groups of dogs the dose responses were then studied against background intravenous infusions of urecholine (10, 20, 40, and 80 mug/kg-h). Vagotomy acted as a competitive inhibitor (Km doubled from 14 to 29 mug/kg-h, while Vmax was unchanged) and this effect could be reversed by smaller than 10 mug urecholine/kg-h. In both groups increasing backgrounds of urecholine increased Vmax from similar to 14 meq H+/30 min to similar to 23-24 meq/30 min and decreased histamine km from 14 mug/kg-h to about 1-2 mug/kg-h. Both changes were log linear. The effects of urecholine on histamine-stimulated H+ secretion thus showed synergism (decreased Km) and potentiation (increased Vmax), the former interpreted as a cholinergic effect on the parietal cell histamine receptors and the latter as the probable existence of spare cholinergic receptors not (normally) accessible to histamine. There were no intrinsic qualitative or quantitative differences in these responses between the vagotomized and the innervated stomachs.

The Interaction of Histamine with Gastrin and Carbamylcholine on Oxygen Uptake by Isolated Mammalian Parietal Cells

“…Underlying this confusion is our lack of understanding of the mechanisms of these interactions. Emphasis has been placed in previous considerations of these interactions upon whether a combination of agents enhances the sensitivity (a decrease in the D50, termed alternatively potentiation [15] and synergism [16]) or enhances the maximal response (termed alternatively effication [15] and potentiation [16] In a previous study, histamine, gastrin, and cholinergic agents were found to stimulate oxygen uptake by isolated mammalian parietal cells (3). The isolated parietal cell appeared to have specific receptors for each of these three secretagogues in that anticholinergics and H2-receptor antagonists were specific for the actions of cholinergic agents and histamine respectively, and neither of these inhibitors altered the small direct response to gastrin (3).…”

“…Furthermore the presence of phosphodiesterase inhibition by IMX did not alter these findings with carbamylcholine and gastrin. It (16,(21)(22)(23)(24)(25); however, interactions demonstrated in this manner are species dependent and variable in magnitude (15,(26)(27)(28). A dramatic demonstration of secretagogue interactions has been made in studies with the ex vivo canine stomach preparation where marked potentiation was found between histamine and pentagastrin, between histamine and bethanechol, and between pentagastrin and bethanechol (29,30).…”

Stimulation of Gastrin Release and Gastric Secretion: Effect of Bombesin and a Nonapeptide in Fistula Dogs with and without Fundic Vagotomy

“…As with other non-cholinergic stimuli (17,18), secretion of pepsin was very low after vagotomy (< 10% of maximum). The lower dose of nonapeptide gave a particularly low pepsin output (<2% of maximum), with pepsin concentrations about 100 PU/ml.…”