This program will develop the Conus system as a general source of novel peptide ligands. The pace with which molecular genetics continues to define new molecular forms of cell surface receptors and ion channels is constantly accelerating; the need to characterize the functional biology of each of these newly-defined receptor subtypes increases correspondingly. Thus, agents which can disrupt the function of specific receptor subtypes are urgently required; this program aims to provide such subtype-discriminating ligands using peptides from Conus. The program supports three scientific cores: (a) a Conus venom resource core, which includes a molecular biology component, (b) a peptide sequencing and synthesis core and (c) an electrophysiology core. Together these cores support a core peptide discovery program to develop new conus peptide ligands. The program consists of three major projects, each divided into three subprojects. The goal of the projects is to study three important classes of receptor targets for which a well-developed set of Conus peptide probes are already available. The focus of each project is: Project I - omega-conotoxins and Ca++ channels; Project II - Cholinergic Conus peptides and nicotinic acetylcholine receptors and Project III - Conantokins and NMDA receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM048677-03
Application #
2186191
Study Section
Special Emphasis Panel (SSS (P2))
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Utah
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Hone, Arik J; McIntosh, J Michael (2018) Nicotinic acetylcholine receptors in neuropathic and inflammatory pain. FEBS Lett 592:1045-1062
Hone, Arik J; Talley, Todd T; Bobango, Janet et al. (2018) Molecular determinants of ?-conotoxin potency for inhibition of human and rat ?6?4 nicotinic acetylcholine receptors. J Biol Chem 293:17838-17852
Banala, Sambashiva; Arvin, Matthew C; Bannon, Nicholas M et al. (2018) Photoactivatable drugs for nicotinic optopharmacology. Nat Methods 15:347-350
Hone, Arik J; Servent, Denis; McIntosh, J Michael (2018) ?9-containing nicotinic acetylcholine receptors and the modulation of pain. Br J Pharmacol 175:1915-1927
Espino, Samuel S; Robinson, Samuel D; Safavi-Hemami, Helena et al. (2018) Conopeptides promote itch through human itch receptor hMgprX1. Toxicon 154:28-34
Richter, Katrin; Sagawe, Sabrina; Hecker, Andreas et al. (2018) C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation. Front Immunol 9:1604
Hiller, Sebastian Daniel; Heldmann, Sarah; Richter, Katrin et al. (2018) ?-Nicotinamide Adenine Dinucleotide (?-NAD) Inhibits ATP-Dependent IL-1? Release from Human Monocytic Cells. Int J Mol Sci 19:
Peng, Can; Yan, Yijin; Kim, Veronica J et al. (2018) Gene editing vectors for studying nicotinic acetylcholine receptors in cholinergic transmission. Eur J Neurosci :
Chen, De-Jie; Gao, Fen-Fei; Ma, Xiao-Kuang et al. (2018) Pharmacological and functional comparisons of ?6/?3?2?3-nAChRs and ?4?2-nAChRs heterologously expressed in the human epithelial SH-EP1 cell line. Acta Pharmacol Sin 39:1571-1581
Siebers, Kathrin; Fink, Bijan; Zakrzewicz, Anna et al. (2018) Alpha-1 Antitrypsin Inhibits ATP-Mediated Release of Interleukin-1? via CD36 and Nicotinic Acetylcholine Receptors. Front Immunol 9:877

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