Bombesin: Action on Gut Hormones and Calcium in Man*

Abstract

Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.

Gastric acid secretion, intraduodenal pH and gastroenteropancreatic hormone release to bombesin in antrocolic transposition dogs.

“…The fact that motilin, insulin and glucagon levels increased during and after bombesin stimulation in both groups is in agreement with previous results in man (Ghatei et al 1982;Bruzzone et al 1983) and in dogs (Schusdziarra et al 1980;McDonald et al 1981;`Taysse et al 1981;McDonald et al 1983). A rise in insulin is not secondary to a rise in glucose, since the plasma glucose does not increase.…”

Protein kinase C-mediated negative-feedback inhibition of unstimulated and bombesin-stimulated polyphosphoinositide hydrolysis in Swiss-mouse 3T3 cells

“…The best characterized of the mammalian peptides are gastrin-releasing peptide, originally purified from pig gastric tissue (McDonald et al, 1979), and the neuromedins B and C, from pig spinal cord (Minamino et al, 1983(Minamino et al, , 1984. Peptides of the bombesin family elicit a wide range of physiological responses, including smoothmuscle contraction (Minamino et al, 1983(Minamino et al, , 1984 and the release of several peptide hormones, including gastrin, cholecystokinin, prolactin and growth hormone (Rivier et al, 1978;Walsh et al, 1979;McDonald et al, 1979;Ghatei et al, 1982;Westendorf & Schonbrunn, 1982). In addition to these acute responses, repeated administration of bombesin to rats has been shown to cause pancreatic (Lezoche et al, 1981) and gastric cell (Lehy et al, 1983) hyperplasia.…”

Tyrosine 220 in the 5th Transmembrane Domain of the Neuromedin B Receptor Is Critical for the High Selectivity of the Peptoid Antagonist PD168368

“…These peptides mediate a spectrum of biological activities by binding to two structurally and pharmacologically distinct receptors, the NMB receptor (NMBR) and GRP receptor (GRPR) (19,20). These peptides have important effects in the central nervous system including thermoregulation (21), satiety (22), control of circadian rhythm (23), and in peripheral tissues causing stimulation of gastrointestinal hormone release (18,24,25), activation of macrophages (26), and effects on development (27,28). These peptides also have potent growth effects causing proliferation of normal cells (18,29) and various tumor cell lines (18,30).…”