Stimulation of pepsinogen release from isolated gastric glands by cholecystokininlike peptides.

Gastric glands isolated from rabbit stomach were employed to study the regulation of pepsinogen secretion by peptide hormones. Cholecystokinin octapeptide (CCK-OP) stimulated pepsinogen secretion with an ED50 of about 1 nM. Caerulein was as effective as CCK-OP but less potent (ED50, 10 nM). Gastrin (HG-17) was found to be a weak stimulus, being only about 20% as effective as CCK-OP or caerulein. Sulfation of CCK-OP and caerulein was found to be important for potency but did not alter efficacy. Peptide stimulation of pepsinogen secretion was unaffected by cimetidine, atropine, or propranolol. Combinations of peptides resulted in less-than-additive responses, as did the combination of peptides with carbachol. In contrast, combination of peptides with isoproterenol resulted in additive responses. Accumulation of the weak base aminopyrine was used to measure acid formation by the gastric glands. The peptides gastrin, CCK-OP, and caerulein were found to be equally effective in stimulating acid formation. The peptide stimulation of pepsinogen secretion was inhibited by dibutyryl cGMP, whereas stimulation of acid formation was not inhibited by the cyclic nucleotide. The results indicate that gastric glands contain at least two peptide receptors distinguishable by sensitivity to dibutyryl cGMP. The peptide receptor associated with pepsinogen secretion appears to be selective for CCK relative to gastrin.