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.