Mechanisms of Stimulatory Effect of Neuromedin C on Pancreatic Exocrine Secretion in Conscious Rats

Abstract

The mechanisms of the stimulatory effect of the bombesin-like peptide neuromedin C on pancreatic exocrine secretion were examined in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately. Intravenous infusion of 0.35 nmoykg/h of neuromedin C significantly increased the secretions of pancreatic bicarbonate and protein, and transiently increased the plasma cholecystokinin (CCK) concentration. The increase in pancreatic secretion persisted for 90 min, whereas the increase in plasma CCK was observed only after 15 and 30 min from the beginning of neuromedin C infusion. Intravenous infusion of CR-1409, a specific CCK-receptor antagonist, inhibited, but did not abolish, the protein secretion stimulated by neuromedin C. Intraduodenal infusion of a potent proton pump inhibitor, omeprazole, suppressed, but did not abolish, protein secretion induced by neuromedin C. Omeprazole abolished the increase in bicarbonate secretion produced by neuromedin C. These results indicate that neuromedin C induces release of CCK and that its induction of pancreatic hypersecretion is due to both its direct effect and CCK. The results also suggest that gastric hypersecretion may have a role in the bicarbonate hypersecretion induced by neuromedin C.

A single in vivo administration of bombesin antagonist RC-3095 reduces the levels and mRNA expression of epidermal growth factor receptors in MXT mouse mammary cancers

“…Infusion (i.v.) of neuromedin C to rats increases plasma cholecystokinin levels within 15-30 min (25). The perfusion of isolated stomach by way of the celiac artery increases somatostatin release with a peak at 4 min from the start of infusion (26).…”

“…Numerous complex pharmacological effects of BN͞GRP are due to both direct and indirect mechanisms of action and depend on the species studied and the route of administration (3). Various studies show that the metabolic effects of BN͞ GRP and their antagonists appear very rapidly, but are relatively short lasting (24)(25)(26)(27)(28)(29)). An i.v.…”

Regulation of Pancreatic Exocrine Function in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats without Gene Expression of Cholecystokinin-A Receptor.

“…Onthe other hand, the responses of protein secretion to neuromedin C and 2DGwere significantly lower in OLETFthan in LETOrats. There are reports (24)(25)(26) that administration of a memberof the gastrin releasing peptide (GRP) family, including neuromedin C, stimulates pancreatic protein secretion directly and indirectly via CCKrelease. In the present study, we did not measure the plasma CCKlevel after neuromedin C injection, but we found previously (1) that CCK release produced by bile-pancreatic juice diversion is not impaired in OLETFrats.…”