1. Pharmacological profiles of two bombesin analogues in cells transfected with human neuromedin B receptors.
- Author
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Ryan RR, Taylor JE, Daniel JL, and Cowan A
- Subjects
- 3T3 Cells drug effects, Animals, Bombesin pharmacology, Bombesin physiology, Cattle, Dose-Response Relationship, Drug, Humans, Mice, Mice, Inbred BALB C, Neurokinin B antagonists & inhibitors, Neurokinin B pharmacology, Oligopeptides pharmacology, Receptors, Bombesin agonists, Transfection, Arachidonic Acid metabolism, Bombesin analogs & derivatives, Calcium metabolism, Neurokinin B analogs & derivatives, Receptors, Bombesin physiology, Somatostatin analogs & derivatives
- Abstract
We examined the effect of two des-Met-bombesin analogues, [(CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]bombesin(6-14) ethylamide (DPDM-bombesin ethylamide), on neuromedin B-induced Ca2+ and [3H]arachidonate release in BALB 3T3 cells transfected with human neuromedin B receptors. ICI 216140 and DPDM-bombesin ethylamide both stimulated Ca2+ mobilisation in a concentration-dependent manner but were less potent and efficacious than neuromedin B. BIM 23042 [D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2], a selective neuromedin B antagonist and [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, a broad-spectrum peptide receptor antagonist inhibited neuromedin B-, ICI 216140 and DPDM-bombesin ethylamide-induced Ca2+ release. Pretreatment of cells with either des-Met-bombesin analogue attenuated neuromedin B-induced Ca2+ elevations, suggesting similar agonist-sensitive Ca2+ pools. The pharmacological profiles revealed from the [3H]arachidonate assay were similar, although ICI 216140 was less potent and efficacious than DPDM-bombesin ethylamide. The data suggest that ICI 216140 and DPDM-bombesin ethylamide behave as agonists at the neuromedin B receptor, perhaps as a consequence of neuromedin B receptor overexpression.
- Published
- 1996
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