J. MICHAEL McINTOSH

Michael McIntosh
e-mail: mcintosh.mike@gmail.com
Professor and Director of Research of Psychiatry
Research Professor of Biology

The McIntosh Lab
Molecular Neuroscience
Neurobiology of Disease
Brain and Behavior
Cellular Neuroscience
B.S. 1983, University of Utah; M.D. 1987, U.C.L.A.; Psychiatry Residency 1987-1991, University of Colorado School of Medicine

RESEARCH:

Molecular Pharmacology of CNS receptors and ion channels

Dr. McIntosh is interested in the neurobiology of CNS disorders. His work is focused on the study of receptor and ion channel pharmacology. At present the research is divided into two main areas: 1) Isolation and characterization of novel conopeptide ligands which can discriminate between closely related receptors and ion channels. These complexes are felt to play a key role in illnesses such as Parkinson's Disease, mood disorders, chronic pain and neuroinflammation; 2) The role of receptors and ion channels in neurotransmitter release. Using electrophysiological and neurochemical techniques, we are examining the modulation of neurotransmitter release by particular receptor subtypes. Development of novel therapeutic agents is one ultimate end point.

Selected Publications:

Hone, A.J., Whiteaker, P., Mohn, J.L., Jacob, M.H., and McIntosh, J.M. (2010) Alexa Fluor 546-ArIB[V11L;V16A] is a potent ligand for selectively labeling alpha7 nicotinic acetylcholine receptors. J Neurochem, Aug;114(4):994-1006. Epub 2010 May 18. PMID: 20492354; Related citations 204632353.

Colomer, C., Olivos-Oré, L.A., Vincent, A., McIntosh, J.M., Artalejo, A.R., and Guérineau, N.C. (2010) Functional characterization of alpha9-containing cholinergic nicotinic receptors in the rat adrenal medulla: implication in stress-induced functional plasticity. J Neurosci, May 12;30(19):6732-6742. PMID: 20463235; Related citations 203635145.

Mayer, A.M., Glaser, K.B., Cuevas, C., Jacobs, R.S., Kem, W., Little, R.D., McIntosh, J.M., Newman, D.J., Potts, B.C., and Shuster, D.E. (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci, Jun;31(6):255-265. Epub 2010 Apr 2.PMID: 20363514; Related citations 20200117

Bordia, T., Campos, C., McIntosh, J.M., and Quik, M. (2010) Nicotinic receptor-mediated reduction in L-DOPA-induced dyskinesias may occur via desensitization. J Pharmacol Exp Ther, Jun;333(3):929-938. Epub 2010 Mar 3.PMID: 20200117; Related citations 198902638.

Brunzell, D.H., Boschen, K.E., Hendrick, E.S., Beardsley, P.M., and McIntosh, J.M. (2010) alpha-Conotoxin MII-sensitive nicotinic acetylcholine receptors in the nucleus accumbens shell regulate progressive ratio responding maintained by nicotine. Neuropsychopharmacology, Feb;35(3):665-673. Epub 2009 Nov 4.PMID: 19890263; Related citations 198123199.

Xiao, C., Nashmi, R., McKinney, S., Cai, H., McIntosh, J.M., and Lester, H.A. (2009) Chronic nicotine selectively enhances alpha4beta2* nicotinic acetylcholine receptors in the nigrostriatal dopamine pathway. J Neurosci, Oct 7;29(40):12428-12439. PMID: 19812319; Related citations 1969371010.

Hone, A.J., Whiteaker, P., Christensen, S., Xiao, Y., Meyer, E.L., and McIntosh, J.M. (2009) A novel fluorescent alpha-conotoxin for the study of alpha7 nicotinic acetylcholine receptors. J Neurochem Oct;111(1):80-89. Epub 2009 Jul 23. PMID: 19650873; Related citations 1964404014.

McIntosh, J.M., Absalom, N., Chebib, M., Elgoyhen, A.B., and Vincler, M. (2009) Alpha9 nicotinic acetylcholine receptors and the treatment of pain. Biochem Pharmacol, Oct 1;78(7):693-702. Epub 2009 May 27. Review. PMID: 19477168; Related citations 1947431517.

Rezvani, K., Teng, Y., Pan, Y., Dani, J.A., Lindstrom, J., García Gras, E.A., McIntosh, J.M., and De Biasi, M. (2009) UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors. J Neurosci, May 27;29(21):6883-6896. PMID: 19474315; Related citations 1944865018.

Azam, L., and McIntosh, J.M. (2009) Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors. Acta Pharmacol Sin, Jun;30(6):771-783. Epub 2009 May 18. Review. PMID: 19448650; Related citations 1914478519.

Perez, X.A., O'Leary, K.T., Parameswaran, N., McIntosh, J.M., and Quik, M. (2009) Prominent role of alpha3/alpha6beta2* nAChRs in regulating evoked dopamine release in primate putamen: effect of long-term nicotine treatment. Mol Pharmacol, Apr;75(4):938-946. Epub 2009 Jan 14. PMID: 19144785.

Olivera, B.M., Quik, M., Vincler, M., and McIntosh, J.M. (2008) Subtype-selective conopeptides targeted to nicotinic receptors: Concerted discovery and biomedical applications. Channels (Austin), Mar 12;2(2).

Brunzel, D.H., Boschen, K.E., Hendrick, E.S., Beardsley, P.M., and McIntosh, J.M. (2009) Alpha conotoxin MII-sensitive nicotinic acetylcholine receptors in the nucleus accumbens shell regulate progressive ratio responding maintained by nicotine. Neuropsychopharmacology, Feb;35(3):665-673.

Whiteaker, P., Marks, M.J., Christensen, S., Dowell, C., Collins, A.C., and McIntosh, J.M. (2008) Synthesis and characterization of 125I-alpha-conotoxin ArIB[V11L;V16A], a selective alpha7 nicotinic acetylcholine receptor antagonist. J Pharmacol Exp Ther, Jun;325(3):910-919. Epub 2008 Mar 6.

Meyer, E.L., Yoshikami, D., and McIntosh, J.M. (2008) The neuronal nicotinic acetylcholine receptors alpha4* and alpha6* differentially modulate dopamine release in mouse striatal slices. J Neurochem, May;105(5):1761-1769. Epub 2008 Feb 1.

Vincler, M., and McIntosh, J.M. (2007) Targeting the alpha9alpha10 nicotinic acetylcholine receptor to treat severe pain. Expert Opin Ther Targets, Jul;11(7):891-897.

Whiteaker, P., Christensen, S., Yoshikami, D., Dowell, C., Watkins, M., Gulyas, J., Rivier, J., Olivera, B.M., and McIntosh, J.M. (2007) Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist. Biochemistry, Jun 5;46(22):6628-6638. Epub 2007 May 12. Erratum in: Biochemistry. 2007 Jun 5;46(22):6636.

Bordia, T., Grady, S.R., McIntosh, J.M., and Quik, M. (2007) Nigrostriatal damage preferentially decreases a subpopulation of alpha6beta2* nAChRs in mouse, monkey, and Parkinson's disease striatum. Mol Pharmacol, Jul;72(1):52-61. Epub 2007 Apr 4.

Vishwanath, V.A., and McIntosh, J.M. (2006) Synthesis of fluorescent analogs of alpha-conotoxin MII. Bioconjug Chem Nov-Dec;17(6):1612-1617.

Vincler, M., Wittenauer, S., Parker, R., Ellison, M., Olivera, B.M., and McIntosh, J.M. (2006) Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc Natl Acad Sci U S A, Nov 21;103(47):17880-17884. Epub 2006 Nov 13.

Quik, M., and McIntosh, J.M. (2006) Striatal alpha6* nicotinic acetylcholine receptors: potential targets for Parkinson's disease therapy. J Pharmacol Exp Ther, Feb; 316(2):481-489.

Shiembob, D.L., Roberts, R.L., Luetje, C.W., and McIntosh, J.M. (2006) Determinants of alpha-conotoxin BuIA selectivity on the nicotinic acetylcholine receptor beta subunit. Biochemistry, Sep 19;45(37):11200-11207.

Azam, L., and McIntosh, J.M. (2005) Effect of novel alpha-conotoxins on nicotine-stimulated [3H]dopamine release from rat striatal synaptosomes. J Pharmacol Exp Ther., Jan;312(1):231-237.

Luo, S., and McIntosh, J.M. (2004) Iodo-α-conotoxin MI selectively binds the alpha/delta subunit interface of muscle nicotinic acetylcholine receptors. Biochemistry, Jun 1;43(21):6656-6662.

McIntosh, J.M., Azam, L., Staheli, S., Dowell, C., Lindstrom, J.M., Kuryatov, A., Garrett, J.E., Marks, M.J., and Whiteaker, P. (2004) Analogs of α-conotoxin MII are selective for a6-containing nicotinic acetylcholine receptors. Mol Pharmacol., Apr;65(4):944-952.

Quik, M., Bordia, T., Forno, L., and McIntosh, J.M. (2004) Loss of α-conotoxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum. J Neurochem., Feb;88(3):668-679.

Chi, S.W., Kim, D.H., Olivera, B.M., McIntosh, J.M., and Han, K.H. (2004) Solution conformation of α-conotoxin GIC, a novel potent antagonist of α3β2 nicotinic acetylcholine receptors. Biochem J., Jun 1;380(Pt 2):347-352.

Dowell, C., Olivera, B.M., Garrett, J.E., Staheli, S.T., Watkins, M., Kuryatov, A., Yoshikami, D., Lindstrom, J.M., and McIntosh, J.M. (2003) α-conotoxin PIA is selective for α6 subunit-containing nicotinic acetylcholine receptors. J Neurosci., Sep 17;23(24):8445-8452.

McIntosh, J.M., Dowell, C., Watkins, M., Garrett, J.E., Yoshikami, D., and Olivera, B.M. (2002) α-conotoxin GIC from Conus geographus, a novel peptide antagonist of nicotinic acetylcholine receptors. J Biol Chem., Sep 13;277(37):33610-33615.

Champtiaux, N., Han, Z.Y., Bessis, A., Rossi, F.M., Zoli, M., Marubio, L., McIntosh, J.M., and Changeux, J.P. (2002) Distribution and pharmacology of a 6-containing nicotinic acetylcholine receptors analyzed with mutant mice. J. Neurosci., 61(1):230-238.

McIntosh, J.M., and Jones, R.M. (2001) Related Articles, Links Cone venom--from accidental stings to deliberate injection. Toxicon, Oct;39(10):1447-51. Review.

Quik, M., Polonskaya, Y., Kulak, J.M., and McIntosh, J.M. (2001) Vulnerability of 125I-α-conotoxin MII binding sites to nigrostriatal damage in monkeys. J. Neurosci., 21:5494-5500.

Oppenheim, R.W., Prevette, D., D'Costa, A., Wang, S., Houenou, L.J., and McIntosh, J.M. (2000) Reduction of neuromuscular activity is required for the rescue of motoneurons from naturally occurring cell death by nicotinic blocking agents. J. Neurosci., 20:6117-6124.

McIntosh, J.M., Corpuz, G.O., Layer, R.T., Garrett, J.E., Wagstaff, J.D., Bulaj, G., Vyazovkina, A., Yoshikami, D., Cruz, L.J., and Olivera, B.M. (2000) Isolation and characterization of a novel Conus peptide with apparent antinociceptive activity. J. Biol. Chem., 275:32391-32397.

Harvey, S.C., McIntosh, J.M., Cartier, G.E., Maddox, F.N., and Luetje, C.W. (1997) Determinants of specificity for α-conotoxins MII on α3β2 neuronal nicotinic receptors. Mol. Pharmacol., 51:336-342.

Kulak, J.M., Nguyen, T.A., Olivera, B.M., and McIntosh, J.M. (1997) α-Conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes. J. Neuroscience, July, Vol. 17, No. 14.

Cartier, G.E., Yoshikami, D., Gray, W.R., Luo, S., Olivera, B.M., and McIntosh, J.M. (1996) A new α-conotoxin which targets α3β2 nicotinic acetylcholine receptors. J. Biol. Chem., 271:7522-7528.