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

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.