Vasoactive intestinal peptide augmentation of cholecystokinin-8-stimulated pepsinogen secretion: evidence for dual modulation of chief cell function

Pepsinogen (PPG) secretion from chief cells (CC) is dually modulated by adenosine 3':5'-monophosphate (cAMP) and calcium second messenger systems. Vasoactive intestinal peptide (VIP) stimulates cellular function by elevating intracellular levels of cAMP. In contrast, cholecystokinin-8 (CCK-8) acts by producing a rise in intracellular calcium concentration. Consequently, it was the purpose of this study to test whether VIP (acting through cAMP-mediated systems) could augment CCK-8 (acting through calcium-dependent systems)-stimulated PPG secretion. Collagenase dispersed rabbit isolated gastric glands (IGG) were incubated alone (unstimulated) or with secretagogues for 30 min. VIP in graded doses of 10(-11) to 10(-7) M was used alone or in combination with CCK-8 (10(-9) M). PPG levels were determined using an assay based on pepsin hydrolysis of [14C]methemoglobin. Results are expressed as percentage of total pepsinogen (within the IGG) secreted above unstimulated levels. VIP alone (10(-11) to 10(-7)) or CCK-8 alone (10(-9)) did not significantly stimulate PPG secretion (P greater than 0.05). The combination of CCK-8 (10(-9) M) plus VIP (10(-7) M) significantly stimulated PPG secretion above unstimulated levels (P less than 0.05). Thus, the combination of VIP and CCK-8 produced greater PPG secretion than either secretagogue alone. These data support the hypothesis that secretagogues acting through either cAMP or calcium-mediated systems contribute to the regulation of PPG secretion from CC and that the two second messenger systems act in concert achieving at least additive effects.