The inhibitory action of a locally applied antihistamine on canine gastric secretion induced by peripheral parasympathetic stimulation

Abstract

I N a previous paper we have shown that in Heidenhain pouch dogs the secretion of acid in response to histamine can be prevented by irrigating the pouch with an antihistamine (promethazine). We considered this inhibition to be due to specific antagonism between histamine and the antihistamine : but Robertson and Grossman (1952) in similar studies have attributed it to damage of the gastric mucosa caused by the direct irritant action of the antihistamine.In the present paper we present similar studies in which the pouch secretion has been provoked not by histamine but by carbaminoyl-,!?-methyl choline chloride, which stimulates pepsin as well as acid production. We shall show that the anti-histamine selectively inhibits the acid production. We believe that this supports the view that its action is not a non-specific effect but a pharmacological antagonism. METHOD OF STUDYFour dogs with separated pouches of the stomach (Heidenhain type) were used. Animals were fasted for a period of 16 hours before each test. Secretion of juice, rich in acid and pepsin, was stimulated by carbaminoyl-@-methyl choline chloride (Mecothane-Savory & Moore), given by subcutaneous injection in a dose of 0.25 mg. quarter-hourly for a period of 29 hours. During this period juice was collected at 15 minute intervals, the volume measured in ml., and the concentration of free hydrochloric acid determined by titration with decinormal sodium hydroxide, using Topfer's solution (p-dimethyl aminoazobenzine) as indicator. From these values, the output of hydrochloric acid for each 15 minute period was calculated in milliequivalents. During each test in each dog specimens of hourly or half hourly juice were obtained by pooling aliquots of each 15 minute collection. The concentration of pepsin in these pooled samples was estimated by the method of Hunt (1948) using dried human serum as substrate. The peptic activity has been expressed in milligrammes of tyrosine-like substances liberated from the substrate per ml, of juice, and the product of the hourly or half-hourly volume of juice, and its peptic activity represents the output of pepsin in mg. of tyrosine equivalents per hour or half hour.The effect of locally applied antihistamine on the secretory response to mecothane was determined by irrigating the pouch with a solution of promethazine hydrochloride (6 mg. per ml. 0.9 per cent saline) for a half hour period before commencing the mecothane injections. The method of irrigation was as previously described (Kay and Forrest, 1956). Three tests were performed on each of the 4 dogs. In three control experiments on each animal, the pouch was irrigated with 0.9 per cent saline alone. MECOTHANE 0 . 2 5 mqm ocr 15 minutes. OUTPUT OF PEPSIN I : : ] mq. TYROSINE Eqs. 0 VOLUME OF JUICE 2,0 0 ml. 0 -4 0 0 I 2 HOURS FIG. 11z.-The secretory response of a separated gastric pouch in a dog to repeated subcutaneous injections of carbaminoyl-p-methyl choline chloride.In the control studies the acid and pepsin responses to repeated subcutaneous injections of mecotha...

The inhibitory action of locally applied antihistamine on the gastric secretion of acid and pepsin induced by meat and insulin in dogs

“…of pouch secretion (Kay and Forrest, 1956 b) and allows the conclusion to be drawn that the antihistamine selectively inhibits the acid-secreting mechanism. I n the present experiments the small reduction in pepsin output following the promethazine irrigation is adequately accounted for by the reduction in the volume of juice secreted.…”