Abstract

Omega-Conotoxins derived from a variety of Conus species will be used as biological probes to explore the role of voltage-sensitive Ca channels in the mammalian central nervous system. The unusual specificity of omega-conotoxins for calcium channel subtypes and their capacity for biochemical manipulation will be exploited in an examination of calcium channel diversity. The work will focus on the use of a newly discovered peptide from Conus magus, MVIIC, which identifies and defines calcium channel subtypes beyond those targeted by any other known ligand. MVIIC receptor targets will be characterized in competition binding, autoradiographic, and photoaffinity crosslinking studies. One target of the MVIIC peptide is cerebellar """"""""P"""""""" channel subtypes and a comparison with this toxin and the """"""""P"""""""" channel defining ligand omega-agatoxin IVA will be made. In addition, the subset of non-""""""""L"""""""", non-""""""""N"""""""" voltage sensitive calcium channels which modulate neurotransmitter release will be investigated. These studies will attempt to define subunit composition, ligand binding sites, and the modulation of expressed channels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM048677-04
Application #
5212210
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Yan, Yijin; Peng, Can; Arvin, Matthew C et al. (2018) Nicotinic Cholinergic Receptors in VTA Glutamate Neurons Modulate Excitatory Transmission. Cell Rep 23:2236-2244
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

Showing the most recent 10 out of 277 publications