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A synthetic peptide that is a bombesin receptor antagonist

Abstract

The tetradecapeptide bombesin was originally isolated from frog skin1. Bombesin-like peptides have since been detected in mammalian gastrointestinal tract2,3, brain3,4 and lung5,6. These peptides have potent pharmacological effects on the central nervous system7, they cause contraction of intestinal, uterine and urinary tract smooth muscle8; and stimulate the release of other peptides including gastrin2,3,9, cholecystokinin9, motilin9, pancreatic polypeptide , neurotensin9, insulin9,10, enteroglucagon9,10, prolactin11,12 and growth hormone11,12. Specific plasma membrane receptors for bombesin have been demonstrated on pancreatic acinar cells13, brain membranes14 and pituitary cells15. Studies defining the physiological importance of bombesin have been impeded by the lack of a bombesin receptor antagonist. Here we describe experiments which demonstrate that a peptide originally described as a substance P receptor antagonist16, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P, is also a bombesin receptor antagonist. This peptide competitively inhibits the ability of bombesin to stimulate enzyme secretion from dispersed pancreatic acini, and also inhibits the action of other peptides that interact with the bombesin receptor.

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Jensen, R., Jones, S., Folkers, K. et al. A synthetic peptide that is a bombesin receptor antagonist. Nature 309, 61–63 (1984). https://doi.org/10.1038/309061a0

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