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The effects of synthetic porcine gastrin-releasing peptide (pGRP), a recently isolated gut hormone, were studied in isolated mouse pancreatic acini. pGRP was found to exert direct effects on amylase release, 2-deoxyglucose ( [3H] 2DG) uptake, and alpha-aminoisobutyric acid (AIB) uptake. The stimulatory effect of pGRP on amylase release was significant at 100 pM, and maximal at 1 nM. Higher concentrations of pGRP exerted a smaller stimulatory effect on amylase release. pGRP also increased [3H]2DG uptake, exerting a detectable effect at 300 pM, and a maximal effect at 30 nM. In contrast to its stimulatory effect on amylase release and [3H]2DG uptake, pGRP inhibited AIB uptake. A significant inhibitory effect on AIB uptake occurred at 100 pM, and a maximal inhibitory effect occurred at 3 nM. Dose-response curves of pGRP for amylase release and AIB uptake were found to be biphasic. Bombesin was also found to stimulate amylase release with a biphasic dose-response curve in mouse acini. Both cholecystokinin (CCK) octapeptide and the cholinergic analog carbachol exerted similar effects in isolated mouse acini. However, the effects of pGRP were not inhibited by either dibutyryl cyclic guanosine 3',5'-monophosphate or atropine, whereas the effects of CCK octapeptide were inhibited by dibutyryl cyclic guanosine 3',5'-monophosphate and the effects of carbachol were inhibited by atropine. These results indicate that pGRP can mimic the biological effects of CCK and acetylcholine, but that its actions are probably mediated via a separate class of receptors in mouse acini.
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