In vivo observations have suggested that acid secretion may potentiate pepsinogen release. We measured pepsinogen and acid secretion by guinea pig fundic mucosal sheets stimulated by 10-4 M histamine, 10-8 and 10-9 M cholecystokinin, and 3 × 10-7 M carbamylcholine and then investigated the effects of 10-4 M omeprazole on basal, carbacholstimulated, and cholecystokinin-stimulated secretion. Histamine increased basal acid secretion fivefold (p < 0.01) without altering pepsinogen secretion. Cholecystokinin did not stimulate acid secretion but increased pepsinogen secretion by factors of 23.1 at 10-8 M and 9.1 at 10-9 M (both p < 0.01). The combination of 10-4 M histamine and 10-9 M cholecystokinin increased acid secretion 3.5-fold and pepsinogen secretion 6.4-fold, statistically equivalent to the sum of the effects of histamine and cholecystokinin alone. Carbachol increased acid secretion and pepsinogen secretion by factors of 4.0 and 10.9, respectively (both p < 0.01). Pretreatment with 10-4 M omeprazole abolished basal and carbachol-stimulated acid secretion. However, pepsinogen secretion was unaffected (p > 0.05). Furthermore, omeprazole-treated tissues increased pepsinogen secretion by factors of 10.0 with 3 × 10-7 M carbachol and 9.1 with 10-9 M cholecystokinin (both p < 0.01). Thus, basal and secretagogue-stimulated pepsinogen secretion appear independent of acid secretion in intact guinea pig mucosa.
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