Showing papers in "British journal of pharmacology and chemotherapy in 1954"

The effect of intravenous infusions of histamine on the urinary histamine and on gastric secretion in man.

Abstract: When histamine is infused intravenously in man at a rate that produces distinct pharmacological effects, it can be easily detected in the urine but not in the venous plasma (Adam, 1950). This author estimated the urinary histamine by a simplified method based on that described by Anrep, Ayadi, Barsoum, Smith, and Talaat (1944). It was possible by this method to follow the excretion when 3.3 mg. of histamine base was infused intravenously, but not the normal or basal excretion of free histamine in the urine. Roberts and Adam (1950) have since shown by a new method that free histamine appears continuously and in measurable amounts in the urine of healthy men, and suggested that the immediate source of this histamine was the blood plasma. The aim of the present work was to obtain further evidence in support of this assumption by following the effect of intravenous infusions of histamine on the urinary excretion of free histamine and on the acid gastric secretion. It was possible in this way to measure the proportion of the drug excreted during the infusion of small doses and to relate the amount excreted to the effect of the infusion on the acid gastric secretion. Since it was not possible to detect free histamine in the plasma by direct methods, the acid gastric secretion was used as a measure of the concentration of free histamine in the circulating blood (Ivy and Javois, 1924; Kalk, 1929; Ungar, 1935; Feldberg and Holmes, 1941; Emmelin, Kahlson, and Wicksell, 1941; Grob, Lilienthal, and Harvey, 1947). Incidental observations were made on the histamine content of the gastric juice. The doseresponse relationship of histamine to the acid secretion of the stomach was also investigated, but the results will be reported elsewhere. Three healthy men, designated as W.I.C., J.A.S., and A.A.G., each received a series of histamine infusions, and the free histamine was estimated in samples of the urine, venous blood plasma and gastric juice. The doses infused were in the range that produced graded effects on the acid gastric secretion. Infusions with the lower doses were symptomless, yet they produced a distinct stimulation of the acid secretion and a measurable increase in the excretion of histamine in the urine.