title: Regulation and signaling of human bombesin receptors and their  biological effects.
abstract: OBJECTIVE
  This review will highlight recent advances in the understanding of molecular mechanisms by which mammalian bombesin receptors are regulated and which intracellular signaling pathways have been characterized to mediate agonist-dependent receptor biological effects.
  
  
  RESULTS
  Mammalian bombesin receptors have been demonstrated to be involved in a larger array of physiological and pathophysiological conditions than previously reported. Pharmacological experiments in vitro and in vivo as well as utilization of animals genetically deficient of the gastrin-releasing peptide receptor demonstrated roles in memory and fear behavior, lung development and injury, small intestinal cell repair, autocrine tumor growth, and mediating signals for pruritus and penile reflexes. Intracellular signaling studies predominantly of the gastrin-releasing peptide receptor owing to its frequent overexpression in some human malignancies showed that PI3 kinase activation is an important mechanism of cell proliferation. Tumor cell treatment including gastrin-releasing peptide receptor antagonists combined with inhibition of epidermal growth factor receptor resulted in an additive effect on blocking cell proliferation. Novel molecular mechanisms of the orphan bombesin receptor subtype-3 and gastrin-releasing peptide receptor gene regulation have been elucidated.
  
  
  CONCLUSIONS
  Inhibition of gastrin-releasing peptide receptor signaling in human malignancies represents an attractive target for pharmacological treatment. Novel functions of bombesin related peptides have been identified including processes in the central nervous system, lung and intestinal tract.
authors.affiliation: Boston University School of Medicine, Section of Gastroenterology, Boston, MA 02118, USA. christian.weber@bmc.org
authors.forename: H Christian
authors.initials: HC
authors.lastname: Weber
mesh_terms: D000818:Animals; D019886:Gastrin-Releasing Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D008297:Male; D008322:Mammals; D009369:Neoplasms / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000503:physiopathology; D018004:Receptors, Bombesin / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide