Bombesin receptor structure and expression in human lung carcinoma cell lines

J Cell Biochem Suppl. 1996;24:237-46. doi: 10.1002/jcb.240630519.

Abstract

Mammalian bombesin-like peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) are regulatory neuropeptides involved in numerous physiologic processes, and have been implicated as autocrine and/or paracrine growth factors in human lung carcinoma. Three structurally and pharmacologically distinct bombesin receptor subtypes have been isolated and characterized: the gastrin releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). The three receptors are structurally related, sharing about 50% amino acid identity. They are members of the G-protein coupled receptor superfamily with a seven predicted transmembrane segment topology characteristic of receptors in this family. The signal transduction pathway for GRP-R and NMB-R involves coupling to a pertussis-toxin insensitive G-protein, activation of phospholipase C (PLC), generation of inositol trisphosphate (IP3), release of intracellular calcium, and activation of protein kinase C. While all three bombesin receptors are activated by bombesin agonists, GRP-R, NMB-R, and BRS-3 have very different affinities for the mammalian bombesin-like peptides GRP and NMB, as well as bombesin receptor antagonists. The three bombesin receptor subtypes are expressed in an overlapping subset of human lung carcinoma cell lines. Any therapeutic strategy based on modulation of bombesin growth responses in human lung carcinoma would be well served to take into account the pharmacologic heterogeneity of the relevant receptors.

Publication types

  • Comparative Study

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Bombesin / pharmacology
  • Bombesin / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cytoskeleton / drug effects
  • GTP-Binding Proteins / metabolism
  • Gastrin-Releasing Peptide
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / classification
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neurokinin B / analogs & derivatives
  • Neurokinin B / physiology
  • Peptides / physiology
  • Protein Conformation
  • Receptors, Bombesin / chemistry
  • Receptors, Bombesin / classification
  • Receptors, Bombesin / drug effects
  • Receptors, Bombesin / genetics
  • Receptors, Bombesin / metabolism*
  • Sequence Alignment
  • Sequence Homology
  • Signal Transduction
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Xenopus laevis

Substances

  • Neoplasm Proteins
  • Peptides
  • Receptors, Bombesin
  • Gastrin-Releasing Peptide
  • Neurokinin B
  • neuromedin B
  • GTP-Binding Proteins
  • Bombesin