A Working Hypothesis for Urecholine Effects on Histamine Stimulation of Gastric Secretion

Abstract

Hirschowitz, B. I. & Hutchison, G. A. A working hypothesis for urecholine effects on histamine stimulation of gastric secretion. Scand. J. Gastroent, 1973, 8, 569-576

Gastric juice volume, H and Cl secreted during dose-response studies in 5 dogs with gastric fistula with histamine alone (2-125 μg/kg. hr, each dose given separately for 4½ hrs) with urecholine alone (10-80 μg/kg. hr) and with histamine (2-50 μg/kr. hr) given against a constant dose background of urecholine, 40 μg/kg. hr, could be described by kinetics conforming to Michaelis-Menten models. Urecholine produced both potentiation of the histamine dose response (increased Vmax), as well as synergism (multiplying the effect of histamine). These changes could be described by introducing 2 new terms (x, y) into the equation V = Vm — be^-cs to give it the form V = (Vm + x) – be^-eys where V = observed response, S dose of stimulant (histamine), Vmax = calculated maximal response. For the dose of urecholine used here, Vmax for peak H⁺ output was increased by 32% from 35 to 46.3 mEq/hr, while the effect of histamine was multiplied 3.0 times at all doses. Comparable effects were seen on water and Cl. Potentiation is explained by postulating spare cholinergic receptors and the synergism by an effect of acetyl-choline which regulates the sensitivity of the receptor to histamine. This model may be used to explain the effects of urecholine, vagotomy and anticholinergics on histamine dose response. The effect on pepsin secretion was only additive and thus different from those effects noted on electrolyte secretion.

Key-words::

• Dose responses
• fistula dogs
• gastric juice H, Cl
• kinetics
• Km
• pepsin
• potentiation
• synergism
• V_max