Trepel J B, Moyer J D, Cuttitta F, Frucht H, Coy D H, Natale R B, Mulshine J L, Jensen R T, Sausville E A
NCI-Navy Medical Oncology Branch, Bethesda, Maryland.
Biochem Biophys Res Commun. 1988 Nov 15;156(3):1383-9. doi: 10.1016/s0006-291x(88)80785-x.
The human small cell lung carcinoma (SCLC) cell line NCI-H345 constitutively produces gastrin-releasing peptide (GRP), a peptide homologous to the mitogen bombesin. In addition, NCI-H345 cells express bombesin receptors and respond to bombesin with rapid activation of phospholipase C and mobilization of intracellular Ca2+. Treatment of NCI-H345 cells with a novel potent bombesin receptor antagonist [Leu13-psi-CH2NH-Leu14]bombesin blocked the increase in phosphatidylinositol turnover and cytoplasmic free Ca2+ ([Ca2+]i) stimulated by bombesin. Furthermore [Leu13-psi-CH2NH-Leu14]bombesin inhibited NCI-H345 colony formation in defined semisolid medium in the absence of exogenous GRP. The rapid, hormone-induced accumulation of inositol(1,4,5)trisphosphate was markedly more sensitive to antagonist inhibition than the hormone-induced Ca2+ transient, the sustained accumulation of inositol monophosphates, or colony formation in soft agarose. These data demonstrated inhibition of transmembrane signals associated with autocrine growth control in SCLC by a novel peptide receptor antagonist.
人小细胞肺癌（SCLC）细胞系NCI - H345持续产生胃泌素释放肽（GRP），这是一种与促有丝分裂剂铃蟾肽同源的肽。此外，NCI - H345细胞表达铃蟾肽受体，并对铃蟾肽作出反应，迅速激活磷脂酶C并动员细胞内的Ca2 +。用新型强效铃蟾肽受体拮抗剂[Leu13 - psi - CH2NH - Leu14]铃蟾肽处理NCI - H345细胞，可阻断铃蟾肽刺激的磷脂酰肌醇周转率增加和细胞质游离Ca2 +（[Ca2 +]i）增加。此外，在没有外源性GRP的情况下，[Leu13 - psi - CH2NH - Leu14]铃蟾肽抑制了NCI - H345在特定半固体培养基中的集落形成。激素诱导的肌醇（1,4,5）三磷酸的快速积累比激素诱导的Ca2 +瞬变、肌醇单磷酸的持续积累或软琼脂糖中的集落形成对拮抗剂抑制更为敏感。这些数据证明了一种新型肽受体拮抗剂对SCLC中与自分泌生长控制相关的跨膜信号的抑制作用。
