AJP - Gastrointestinal and Liver Physiology, Vol 252, Issue 3 439-G442, Copyright © 1987 by American Physiological Society

ARTICLES

[D-Phe12]bombesin analogues: a new class of bombesin receptor antagonists

P. Heinz-Erian, D. H. Coy, M. Tamura, S. W. Jones, J. D. Gardner and R. T. Jensen

Previous attempts to develop analogues of bombesin that function as specific receptor antagonists have been unsuccessful. Alteration of the histidine in luteinizing hormone releasing factor has resulted in analogues that function as competitive antagonists. In the present study we have used a similar strategy and altered the histidine in bombesin. [D-Phe12]bombesin, [D-Phe12,Leu14]bombesin, and [Tyr4,D-Phe12]bombesin did not stimulate amylase release from guinea pig pancreatic acini when present alone, but each analogue inhibited bombesin-stimulated secretion. For each analogue, detectable inhibition occurred at 1 microM and half-maximal inhibition at 4 microM. Each analogue inhibited amylase release by bombesin and other agonists that stimulate secretion by interacting with bombesin receptors. The analogues of bombesin did not alter stimulation by substance P or other agonists that interact with other receptors. The inhibition of the action of bombesin was competitive with Schild plots having slopes of 1.0. Each analogue also inhibited binding of 125I-labeled [Tyr4]bombesin but not 125I-labeled substance P. These results demonstrate that [D-Phe12] analogues of bombesin function as bombesin receptor antagonists and are the only bombesin receptor antagonists that interact only with the bombesin receptor. Because of their specificity, these analogues may prove useful for defining the role of bombesin in various physiological or pathological processes.

This article has been cited by other articles:

				M. Altstein, O. Ben-Aziz, S. Daniel, I. Schefler, I. Zeltser, and C. Gilon Backbone Cyclic Peptide Antagonists, Derived from the Insect Pheromone Biosynthesis Activating Neuropeptide, Inhibit Sex Pheromone Biosynthesis in Moths J. Biol. Chem., June 18, 1999; 274(25): 17573 - 17579. [Abstract] [Full Text] [PDF]

				S. A. Mantey, H. C. Weber, E. Sainz, M. Akeson, R. R. Ryan, T. K. Pradhan, R. P. Searles, E. R. Spindel, J. F. Battey, D. H. Coy, et al. Discovery of a High Affinity Radioligand for the Human Orphan Receptor, Bombesin Receptor Subtype 3, Which Demonstrates That It Has a Unique Pharmacology Compared with Other Mammalian Bombesin Receptors J. Biol. Chem., October 10, 1997; 272(41): 26062 - 26071. [Abstract] [Full Text] [PDF]