Abstract

Recent studies show that gastrointestinal hormones/growth factors may stimulate cell growth by stimulating multiple intracellular tyrosine phosphorylation (TyrP) signaling cascades. However at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades in GI tissues. Our studies have been in two general areas, which include studies of intracellular signaling cascades primarily by tyrosine kinases and studies of tumoral growth attempting to develop novel agents for growth inhibition. Recent studies show that gastrointestinal hormones, similar to growth factors, may stimulate cell growth/cell signaling by stimulating multiple intracellular tyrosine phosphorylation (TyrP) cascades. Whereas these cascades have been extensively investigated with growth factors, little is known in this area with may gastrointestinal hormones. The goal of these studies is to clarify this area primarily concentrating on cholecystokinin receptor cascades and bombesin receptor activation using primarily pancreatic acini as a model natural cell system. Studies involving phosphorylation of PKD1, GAB1, AKT have been completed and studies of PKC theta are in process. Novel cytotoxic agents coupled to different GI hormones have been described.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK053101-20
Application #
7734180
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2008
Total Cost
$365,344
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

González, Nieves; Mantey, Samuel A; Pradhan, Tapas K et al. (2009) Characterization of putative GRP- and NMB-receptor antagonist's interaction with human receptors. Peptides 30:1473-86
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
Gonzalez, Nieves; Moody, Terry W; Igarashi, Hisato et al. (2008) Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes 15:58-64
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
Gonzalez, Nieves; Hocart, Simon J; Portal-Nunez, Sergio et al. (2008) Molecular basis for agonist selectivity and activation of the orphan bombesin receptor subtype 3 receptor. J Pharmacol Exp Ther 324:463-74
Berna, Marc J; Tapia, Jose A; Sancho, Veronica et al. (2007) Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential. Curr Opin Pharmacol 7:583-92
Berna, Marc J; Hoffmann, K Martin; Tapia, Jose A et al. (2007) CCK causes PKD1 activation in pancreatic acini by signaling through PKC-delta and PKC-independent pathways. Biochim Biophys Acta 1773:483-501
Berna, Marc J; Jensen, Robert T (2007) Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases. Curr Top Med Chem 7:1211-31
Moody, Terry W; Mantey, Samuel A; Fuselier, Joseph A et al. (2007) Vasoactive intestinal peptide-camptothecin conjugates inhibit the proliferation of breast cancer cells. Peptides 28:1883-90
Corleto, V D; Severi, C; Romano, G et al. (2006) Somatostatin receptor subtypes mediate contractility on human colonic smooth muscle cells. Neurogastroenterol Motil 18:217-25

Showing the most recent 10 out of 27 publications