Two bombesin analogues discriminate between neuromedin B- and bombesin-induced calcium flux in a lung cancer cell line.

Abstract

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.

• Authors: R R Ryan, J L Daniel, A Cowan
• Journal: Peptides (Peptides) 1993 Nov-Dec Vol. 14 Issue 6 Pg. 1231-5 ISSN: 0196-9781 [Print] United States
• PMID: 8134305 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Oligopeptides
• Peptide Fragments
• bombesin (6-14)-ethylamide, Phe(6)-des-Met(14)-
• ICI 216140
• Neurokinin B
• neuromedin B
• Bombesin
• Calcium

Topics

• Amino Acid Sequence
• Bombesin (analogs & derivatives, antagonists & inhibitors, pharmacology, physiology)
• Calcium (metabolism)
• Carcinoma, Small Cell (metabolism)
• Humans
• Lung Neoplasms (metabolism)
• Molecular Sequence Data
• Neurokinin B (analogs & derivatives, antagonists & inhibitors, physiology)
• Oligopeptides (pharmacology)
• Peptide Fragments (pharmacology)
• Tumor Cells, Cultured