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.