Two bombesin analogues discriminate between neuromedin B- and bombesin-induced calcium flux in a lung cancer cell line.
We examined the profile of two bombesin (BN) antagonists, (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]BN(6-14)ethylamide (DPDM-BN EA), against neuromedin B-induced Ca2+ mobilization in the small cell lung cancer (SCLC) line NCI-H345. Neuromedin B (NMB), a BN-like peptide sharing sequence homology with ranatensin, elicited a concentration-dependent Ca2+ release (in part) from intracellular stores. Sequential addition of NMB attenuated Ca2+ mobilization. Desensitization occurred between BN and NMB; depletion of intracellular Ca2+ is a likely mechanism because thapsigargin stimulated Ca2+ release after a maximally desensitizing dose of NMB. ICI 216140 and DPDM-BN EA competitively inhibited BN-induced Ca2+ transients. In contrast, these compounds antagonized NMB-stimulated Ca2+ transients in a noncompetitive manner. The pharmacological profiles obtained support receptor heterogeneity for BN-like peptides on this SCLC line, underscoring the need for thorough examination of dose-response relationships when investigating effects of BN analogues on intact cells.
Ryan
R R
RR
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140.
Daniel
J L
JL
Cowan
A
A
D000595:Amino Acid Sequence; D001839:Bombesin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D010446:Peptide Fragments; C086327:bombesin (6-14)-ethylamide, Phe(6)-des-Met(14)-; C061858:ICI 216140; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin; D002118:Calcium