Inhibition of Gastric Secretion in Vivo by Iodoacetamide and N-Ethyl Maleimide

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Abstract
The present investigation is an attempt to confirm and amplify in vivo the observation of Davenport that HCl secretion by mouse stomachs in vitro is blocked ‘nearly to zero’ by the irreversible enzyme inhibitors iodo acetamide (IAA) and N-ethyl maleimide (NEM). Aqueous solutions of the inhibitor, in various concentrations, were applied topically to canine Heidenhain pouches for a half-hour. In each such experiment, secretory capacity was measured directly before and after such treatment in terms of the output of free HCl (Qhcl, expressed as mEq/2 hr.) following subcutaneous injection of histamine (0.1 mg/kg). In 13 such experiments, the posttreatment Qhcl was zero for at least 4 hours, thus demonstrating inhibition of acid formation in the living pouch dog. Contrary to the results in vitro, secretory response to histamine was complete; also, it recovered markedly within 24 hours, and probably completely within 48 hours following withdrawal of the inhibitor. In these experiments, and also in others in which histamine administration was withheld following application of the inhibitor to the mucosa, there was formed a nonacid viscous fluid (ph above 7.0) which contains hexosamine, other reducing substances, and much protein, and which has a variable buffering power. This material is suspected of being a mixture of gastric mucus, the still hypothetical ‘mucoid secretion’ and serous transudate formed in response to mucosal initiation.