BOMBESIN RECEPTOR STRUCTURE AND EXPRESSION IN HUMAN LUNG-CARCINOMA CELL-LINES

Mammalian bombesin-like peptides gastrin-releasing peptide (GRP) and n euromedin B (NMB) are regulatory neuropeptides involved in numerous ph ysiologic processes, and have been implicated as autocrine and/or para crine growth factors in human lung carcinoma. Three structurally and p harmacologically distinct bombesin receptor subtypes have been isolate d and characterized: the gastrin releasing peptide receptor (GRP-R), t he neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS -3). The three receptors are structurally related, sharing about 50% a mino acid identity. They are members of the G-protein coupled receptor superfamily with a seven predicted transmembrane segment topology cha racteristic of receptors in this family. The signal transduction pathw ay for GRP-R and NMB-R involves coupling to a pertussis-toxin insensit ive G-protein, activation of phospholipase C (PLC), generation of inos itol trisphosphate (IP3), release of intracellular calcium, and activa tion of protein kinase C. While all three bombesin receptors are activ ated by bombesin agonists, GRP-R, NMB-R, and BRS-3 have very different affinities for the mammalian bombesin-like peptides GRP and NMB, as w ell as bombesin receptor antagonists. The three bombesin receptor subt ypes are expressed in an overlapping subset of human lung carcinoma ce ll lines. Any therapeutic strategy based on modulation of bombesin gro wth responses in human lung carcinoma would be well served to take int o account the pharmacologic heterogeneity of the relevant receptors. ( C) 1996 Wiley-Liss, Inc.