title: A novel bombesin receptor antagonist inhibits autocrine signals in a small cell lung carcinoma cell line.
abstract: 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.
authors.affiliation: NCI-Navy Medical Oncology Branch, Bethesda, Maryland.
authors.forename: J B
authors.initials: JB
authors.lastname: Trepel
authors.forename: J D
authors.initials: JD
authors.lastname: Moyer
authors.forename: F
authors.initials: F
authors.lastname: Cuttitta
authors.forename: H
authors.initials: H
authors.lastname: Frucht
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
authors.forename: R B
authors.initials: RB
authors.lastname: Natale
authors.forename: J L
authors.initials: JL
authors.lastname: Mulshine
authors.forename: R T
authors.initials: RT
authors.lastname: Jensen
authors.forename: E A
authors.initials: EA
authors.lastname: Sausville
mesh_terms: D001839:Bombesin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D019886:Gastrin-Releasing Peptide; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D010452:Peptide Biosynthesis; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D019886:Gastrin-Releasing Peptide; D010738:Type C Phospholipases; D001839:Bombesin; D002118:Calcium