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An isolated vascularly perfused stomach for studying drug distribution, metabolism and action in the stomach: acid secretion in response to secretagogues.

Experimental utilization of isolated vascularly perfused rat stomach with retention of the exocrine response to various stimulants was studied. By the inclusion of bovine erythrocytes in the vascular perfusate and by the use of luminal perfusate possessing a suitable buffer capacity, it was found that acid secretion was significantly stimulated by the perfusion of histamine, pilocarpine, cyclic adenosine monophosphate (AMP), dibutyryl cyclic AMP or theophylline. In addition, cimetidine, a histamine H2-receptor antagonist, inhibited histamine-induced acid secretion in a reversible manner. Although tetragastrin stimulated acid secretion in immature rat or guinea pig stomach, it caused little secretory response in adult rat stomach. On the addition of pepstatin, a pepsin inhibitor, to the vascular perfusate, an acid secretion induced by tetragastrin in adult rat stomach was observed. These findings indicate that some changes in gastrin receptors may develop during the maturation process and that gastrin-induced acid secretion is easily altered by peptic activity in the gastric glands of the perfused stomach. The proposed perfusion system should be useful for studying drug distribution, metabolism and action in the stomach.