Ryan R R, Daniel J L, Cowan A
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140.
Peptides. 1993 Nov-Dec;14(6):1231-5. doi: 10.1016/0196-9781(93)90181-f.
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.
我们研究了两种蛙皮素（BN）拮抗剂，即(CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3]（ICI 216140）和[D-Phe6,des-Met14]BN(6-14)乙酰胺（DPDM-BN EA），对小细胞肺癌（SCLC）细胞系NCI-H345中神经介素B诱导的Ca2+动员的作用。神经介素B（NMB）是一种与蛙皮紧张肽具有序列同源性的类BN肽，可（部分）从细胞内储存库中引发浓度依赖性的Ca2+释放。依次添加NMB可减弱Ca2+动员。BN和NMB之间会发生脱敏；细胞内Ca2+耗竭可能是一种机制，因为在给予最大脱敏剂量的NMB后，毒胡萝卜素刺激了Ca2+释放。ICI 216140和DPDM-BN EA竞争性抑制BN诱导的Ca2+瞬变。相比之下，这些化合物以非竞争性方式拮抗NMB刺激的Ca2+瞬变。所获得的药理学特征支持了该SCLC细胞系上类BN肽的受体异质性，强调了在研究BN类似物对完整细胞的作用时，需要彻底检查剂量反应关系。
