Dose-Response Relationship of Graded Doses of Intravenous Histamine Infusion on Gastric Acid Secretion in Man

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Abstract
Dose-response curves for the effect of continuous intravenous infusion of histamine on the gastric acid secretion was obtained in nine healthy volunteers of Indian origin. Each subject was studied with 5 doses (20, 40, 60, 80, and 100 μg/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The plateau of secretion occurred in the 2nd h of infusion. The analysis of variance revealed that acid output significantly increased with increasing dose of histamine; the increase in acid output was significant at all dose levels except between 80 and 100 μg/kg/h. The analysis of data using dose of histamine independent of body weight gave a poorer fit to the regression line than that obtained with histamine dose on the basis of body weight, suggesting that dose of histamine should be administered on the basis of body weight. The estimate of calculated Vmax and the dose of histamine producing a response 50% of Vmax or (Km) by the three different transformations of the Michaelis-Menten equation gave somewhat different values for both these constants. All these were slightly different from direct estimation of Vmax and Km with analysis of curvilinear regression. The linear transformation using the plot of Cs/v versus Cs gave the best results. The double reciprocal plot underestimated both the constants. The value of Km in Indian subjects was almost six times the value in Western subjects, indicating the relative insensitivity of the parietal cells to histamine in our subjects.

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