Abstract

The goal of the research is to gain increased biochemical and molecular understanding of subtypes of NMDA and dopamine receptors. These receptors may be important in understanding the pathophysiology and treatment of illnesses such as schizophrenia and substance abuse, in addition to understanding basic brain processes. The initial focus will be on conotoxins, peptide ligands from the marine snail, I which represent novel tools for studying NMDA and dopamine receptors. One family of conotoxins, known as """"""""conantokins"""""""" appears to have specificity for distinct developmental subtypes of NMDA receptors. Brain slice preparations, autoradioraphic techniques, brain mRNA injected oocytes and crosslinking techniques will be used to explore this hypothesis. A second family of conotoxins appears to target D2 dopamine receptors. These toxins will be purified, biochemically characterized and their receptor specificity determined. Molecular genetic techniques will be used to isolate D2 receptor-targeted peptide genes and define additional D2-specific conotoxin homologs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Unknown (K20)
Project #
5K20MH000929-03
Application #
3088920
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Project Start
1991-07-01
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Harvey, S C; McIntosh, J M; Cartier, G E et al. (1997) Determinants of specificity for alpha-conotoxin MII on alpha3beta2 neuronal nicotinic receptors. Mol Pharmacol 51:336-42
Jacobsen, R; Yoshikami, D; Ellison, M et al. (1997) Differential targeting of nicotinic acetylcholine receptors by novel alphaA-conotoxins. J Biol Chem 272:22531-7
Kulak, J M; Nguyen, T A; Olivera, B M et al. (1997) Alpha-conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes. J Neurosci 17:5263-70
Tavazoie, S F; Tavazoie, M F; McIntosh, J M et al. (1997) Differential block of nicotinic synapses on B versus C neurones in sympathetic ganglia of frog by alpha-conotoxins MII and ImI. Br J Pharmacol 120:995-1000
Craig, A G; Jimenez, E C; Dykert, J et al. (1997) A novel post-translational modification involving bromination of tryptophan. Identification of the residue, L-6-bromotryptophan, in peptides from Conus imperialis and Conus radiatus venom. J Biol Chem 272:4689-98
Pereira, E F; Alkondon, M; McIntosh, J M et al. (1996) Alpha-conotoxin-ImI: a competitive antagonist at alpha-bungarotoxin-sensitive neuronal nicotinic receptors in hippocampal neurons. J Pharmacol Exp Ther 278:1472-83
Terlau, H; Stocker, M; Shon, K J et al. (1996) MicroO-conotoxin MrVIA inhibits mammalian sodium channels, but not through site I. J Neurophysiol 76:1423-9
McIntosh, J M; Hasson, A; Spira, M E et al. (1995) A new family of conotoxins that blocks voltage-gated sodium channels. J Biol Chem 270:16796-802
Martinez, J S; Olivera, B M; Gray, W R et al. (1995) alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity. Biochemistry 34:14519-26
McIntosh, J M; Ghomashchi, F; Gelb, M H et al. (1995) Conodipine-M, a novel phospholipase A2 isolated from the venom of the marine snail Conus magus. J Biol Chem 270:3518-26

Showing the most recent 10 out of 17 publications