Effects of neuromedin B and neuromedin C on exocrine and endocrine rat pancreas

Abstract

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa and show striking sequence homology with bombesin and gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin B and C on exocrine pancreatic function and insulin release have been compared with bombesin and GRP-27 in isolated pancreatic acini and isolated perfused pancreas in rat. Neuromedin B and C as well as bombesin and GRP-27 were able to cause stimulation of amylase release. The relative efficacy of neuromedin B, C, bombesin, and GRP-27 was the same as that of cholecystokinin octapeptide (CCK-8). Bombesin and GRP-27 were equipotent, and both were approximately 15-fold less potent than CCK-8. Neuromedin C was approximately 2-fold more potent, whereas neuromedin B as approximately 10-fold less potent than bombesin and GRP-27. All of these peptides stimulated insulin release that was limited to the first 3 min of a 20-min perfusion. However, GRP-27 and its related peptides were weak stimulants of insulin release compared with their abilities to stimulate exocrine pancreatic secretion. Bombesin and neuromedin B id not stimulate insulin release at doses stimulating pancreatic exocrine secretion. Neuromedin B was also approximately 10-fold less potent than neuromedin C, bombesin, and GRP-27 in eliciting insulin secretion. Because bombesin-like immunoreactivity is found to be present in nerves in the pancreas, neuromedin B and C may be neurotransmitters or neuromodulators and exert a direct local neurocrine action on enzyme secretion by acinar cells and insulin secretion by the islets.

Effect of a new potent CCK antagonist, lorglumide, on caerulein‐ and bombesin‐induced pancreatic secretion and growth in the rat

“…The results of the present investigation confirm the powerful stimulatory effect of both caerulein and bombesin on exocrine pancreatic secretion, already pointed out in different in vitro (Bertaccini, 1976;Gardner & Jensen, 1981;Jensen et al, 1984;Otsuki et al, 1987) and in vivo (Bertaccini, 1976;Namba et al, 1986;Varga et al, 1988a,b) experimental conditions. In our in vitro system, which was used for the first time to assess the pancreatic secretory action of these peptides, caerulein proved to be of equal efficacy compared to bombesin.…”

“…Its potency, however, was one order of magnitude higher than that of bombesin. This potency ratio was comparable to that found in rat (Otsuki et al, 1987) and guinea-pig (Gardner & Jensen, 1981) pancreatic acini. The results obtained with lorglumide demonstrate that this compound is a potent and selective antagonist of CCK-induced amylase release.…”

“…The rats of the remaining three groups were given bombesin (10 Mg kg-) intraperitoneally. This dose of the peptide was chosen because several studies (Gardner & Jensen, 1981;Namba et al, 1986;Otsuki et al, 1987) have shown bombesin to be equally effective, but 10 times less potent than caerulein. Animals of group 4 were pretreated with saline whereas those of groups 5 and 6 were given lorglumide (doses as above).…”

“…In vitro studies have provided conflicting results. Bombesin, has been found to stimulate amylase release from rat (Iwatsuki & Petersen, 1978;Otsuki et al, 1987), guinea-pig (Jensen et al, 1984), mouse (Iwatsuki & Petersen, 1978) and human (Susini et al, 1986) pancreatic acini, whereas it is ineffective in the same dog preparation (Bommelaer et al, 1981).…”

Effects of Neuromedin B on Insulin and Glucagon Release from the Isolated Perfused Rat Pancreas.

“…Concerning pancreatic hormone release, our recent in vivo and in vitro studies have demonstrated that NMB and GRP-10 clearly stimulate insulin release in dogs and that glucagon release was slightly stimulated by higher doses of GRP-10 and not by NMB (Kawai et al, 1988). On the other hand, in isolated perfused rat pancreases the stimulatory effect of NMB and GRP-10 on insulin release was not clear (Otsuki et al, 1987) in contrast to our results with isolated canine pancreas perfusion. Our previous study demonstrated that substance P stimulated insulin release from the isolated perfused canine pancreas and inhibited it from the rat pancreas (Chiba et al, 1985).…”