Characterization And Pharmacology Of Receptors For Gastrointestinal Peptides

Jensen, Robert

Abstract

The pharmacology and molecular pharmacology of various gastrointestinal (GI) peptides are being investigated. Two peptide receptor families investigated during the year are those for bombesin- (Bn) related peptides and for VIP-related peptides. Bn-related peptides (GRP, NMB) interact primarily with three distinct receptors (GRP-R, NMB-R)and the orphan receptor, BRS-3 to mediate a number of effects in the GI tract and central nervous system (CNS). Using information from structure-function studies by us and others we have synthesized high affinity Bn and VIP analogues that were metabolically stable and that be could to cytotoxic agents as well as performed receptor ligand structure function studies to gain insights into the molecular determinants of high affinity receptor interaction. We also studied the signaling cascade for internalization of Bombesin-related peptides because of the importance of this process in mediating cellular uptake that could be used by cytotoxic agents.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK053100-20
• Application #: 7734179
• Support Year: 20
• Fiscal Year: 2008
• Total Cost: $363,922

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases
• Country: United States

Publications

Nuche-Berenguer, Bernardo; Jensen, R T (2015) Gastrointestinal hormones/neurotransmitters and growth factors can activate P21 activated kinase 2 in pancreatic acinar cells by novel mechanisms. Biochim Biophys Acta 1853:2371-82

Alves, Bryce N; Marshall, Kristen; Tamang, David L et al. (2009) Lipid-dependent cytotoxicity by the lipase PLRP2 and by PLRP2-positive cytotoxic T lymphocytes (CTLs). Cell Biochem Funct 27:296-308

Berna, Marc J; Tapia, Jose A; Sancho, Veronica et al. (2009) Gastrointestinal growth factors and hormones have divergent effects on Akt activation. Cell Signal 21:622-38

Alves, Bryce N; Leong, Jeff; Tamang, David L et al. (2009) Pancreatic lipase-related protein 2 (PLRP2) induction by IL-4 in cytotoxic T lymphocytes (CTLs) and reevaluation of the negative effects of its gene ablation on cytotoxicity. J Leukoc Biol 86:701-12

Gonzalez, Nieves; Nakagawa, Tomoo; Mantey, Samuel A et al. (2009) Molecular basis for the selectivity of the mammalian bombesin peptide, neuromedin B, for its receptor. J Pharmacol Exp Ther 331:265-76

Seidita, G; Mirisola, M; D'Anna, R P et al. (2008) Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet 147B:807-13

Igarashi, Hisato; Ito, Tetsuhide; Kuwano-Kojima, Mizuho et al. (2008) Involvement of VPAC1 and VPAC2 receptors in increasing local pancreatic blood flow in anesthetized rats. Pancreas 37:236-8

Moody, Terry W; Pradhan, Tapas; Mantey, Samuel A et al. (2008) Bombesin marine toxin conjugates inhibit the growth of lung cancer cells. Life Sci 82:855-61

Schumann, Michael; Nakagawa, Tomoo; Mantey, Samuel A et al. (2008) Function of non-visual arrestins in signaling and endocytosis of the gastrin-releasing peptide receptor (GRP receptor). Biochem Pharmacol 75:1170-85

Jensen, R T; Battey, J F; Spindel, E R et al. (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev 60:1-42