Dissociation of pepsinogen and acid secretion in the guinea pig

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 x 10(-7) M carbamylcholine and then investigated the effects of 10(-4) M omeprazole on basal, carbachol-stimulated, and cholecystokinin-stimulated secretion. Histamine increased basal acid secretion fivefold (p less than 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 less than 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 less than 0.01). Pretreatment with 10(-4) M omeprazole abolished basal and carbachol-stimulated acid secretion. However, pepsinogen secretion was unaffected (p greater than 0.05). Furthermore, omeprazole-treated tissues increased pepsinogen secretion by factors of 10.0 with 3 x 10(-7) M carbachol and 9.1 with 10(-9) M cholecystokinin (both p less than 0.01). Thus, basal and secretagogue-stimulated pepsinogen secretion appear independent of acid secretion in intact guinea pig mucosa.