Pharmacological profiles of two bombesin analogues in cells transfected with human neuromedin B receptors.
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.
Ryan
R R
RR
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. ryandick@astro.ocis.temple.edu
Taylor
J E
JE
Daniel
J L
JL
Cowan
A
A
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018004:Receptors, Bombesin / Q000819:agonists / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives*; D014162:Transfection
D009842:Oligopeptides; D018004:Receptors, Bombesin; C061858:ICI 216140; D016718:Arachidonic Acid; D013004:Somatostatin; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin; D002118:Calcium