bombesin nonapeptide

Recent studies suggest that different subtypes of receptors may mediate the action of various bombesin-related peptides in different tissues. In the present study the ability of bombesin and its structurally related peptides [litorin, gastrin-releasing peptide (GRP), GRP18-27, neuromedin B, [Leu8]litorin, and bombesin nonapeptide BN(6-14)] to interact with smooth muscle cells isolated from guinea pig stomach was investigated. Each peptide induced a specific contractile response with potencies (D50 in pM) of [Leu8]litorin (0.7) greater than bombesin (1.2) greater than litorin (3) greater than neuromedin B (3.5) = GRP (3.8) = GRP18-27 (3.9) greater than BN(6-14) (70.9). The specific bombesin receptor antagonist psi 13,14-bombesin differed in its potency for inhibiting equipotent concentrations of bombesin, GRP, or neuromedin B, was equipotent for bombesin or GRP (IC50 12.7 and 22.1 nM), and was 11 times less potent for neuromedin B (IC50 234.5 nM), suggesting the presence of subtypes of receptors mediating the action of bombesin-related peptides. To further investigate this possibility, a technique of receptor protection that enables selective preservation of one receptor type was used. GRP or bombesin protected completely the response to GRP or bombesin but abolished the subsequent contractile response to neuromedin B. Neuromedin B, instead, protected only the response to neuromedin B. These results demonstrate that gastric smooth muscle cells possess specific receptors that interact with bombesin-related peptides and that two receptor subtypes mediate the contractile response to these peptides: one subtype is selective for bombesin or GRP, the other for neuromedin B.

The pharmacological activity of two natural bombesin-like peptides, alytesin and litorin, and 25 related synthetic peptides has been compared to that of bombesin. 2 The minimum length of the amino acid chain required for the first appearance of bombesin-like effects was represented by the C-terminal heptapeptide, and the minimum length for maximal effects by the C-terminal nonapeptide. The latter possessed approximately the same activity as bombesin and may be considered a good substitute. 3 Both the tryptophan and histidine residues seemed to be essential for bombesin-like activity. 4 The C-terminal octapeptide was less active than either bombesin or the C-terminal nonapeptide and its action was more rapid in onset and less sustained. 5 Litorin apparently has an intermediate position between bombesin octapeptide and bombesin nonapeptide in the speed and duration of its effects. The relationship between structure and activity is discussed.

Bombesin and a synthetic bombesin nonapeptide were studied by intravenous infusion at a dose of 0.5 microgram.kg-1.h-1 for 4 h in 7 dogs with esophagostomy and gastric fistula. In 3 of the dogs who had highly selective (fundic) vagotomy, mean integrated gastrin output over 4 h was double that in the 4 dogs with vagi intact during both nonapeptide (1,554 vs. 700 pg.ml-1.4 h-1) and bombesin infusion (2,442 vs. 1,440 pg.ml-1.4 h-1). Peak concentrations of serum gastrin reached during bombesin (490 +/- 100 vs. 320 +/- 90) were higher than those during nonapeptide infusion (270 +/- 40 vs. 160 +/- 28 pg/ml) in the vagotomized and intact dogs, respectively. The difference between vagotomized and vagally intact dogs suggests that the fundic vagotomy removed an inhibitor of gastrin release from the innervated antrum. Despite these differences in gastrin release, gastric acid output with the two peptides was the same (49--52 mEq/4 h) whether the fundus was denervated or innervated. This suggests that bombesin may stimulate gastric acid secretion by the release of an additional secretagogue which is not measured by the gastrin assay. Neither of the two inhibitors of gastrin release--antral acidification to pH 1.4 or less or atropine (100 microgram/kg)-- inhibited gastrin release by bombesin, even though the atropine reduced acid output by 80%. Bombesin is a potent gastric stimulus whose action is only partly explained by the measured gastrin release.