Ken Mackie

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University of Washington
School of Medicine
Anesthesiology
ProfessorAppointed: 2000
University of Washington
School of Medicine
Physiology and Biophysics
Adjunct ProfessorAppointed: 2000

Mailing Address

Box 356540
University of Washington
Seattle, Washington 98195
United States

Contact Information

Phone: (206) 616-2669
Fax: (206) 543-2958
kmackie@u.washington.edu

Qualifications

M.D., Yale University, Medicine, 1984.

Expertise and Research Interests

The major focus of my research program is elucidating the cellular actions of cannabinoids in neurons. Our interest in cannabinoid pharmacology comes not only from the social and medicinal uses of cannabis, but also because we have endogenous cannabinoids(e.g., anandamide) and cannabinoid receptors (designated CB1) in our brains. Anandamide and CB1 are two components of a novel neuromodulatory system with a widespread distribution including brain areas involved in learning and memory. The psychoactive effects of cannabinoids are primarily a consequence of the activation of a G protein-coupled receptor (CB1). Cannabinoids acting through CB1 inhibit N and Q type voltage- dependent calcium current and activate an inwardly-rectifying potassium current. Thisprofile of actions suggests that cannabinoids may elicit behavioral effects by decreasing neuronal excitability and neurotransmitter release (presynaptic inhibition). Current work in my laboratory focuses on three main areas. The first is exploring the role of CB1 and calcium channels in presynaptic inhibition using molecular biology, imaging and electrophysiology. The second is determining the coupling mechanism between the CB1 receptor and its effectors, with an emphasis on G proteins and protein phosphorylation. The third is understanding the molecular basis of tolerance to cannabionids. These experiments focus on receptor/effector uncoupling and receptor internalization.

Keywords

COS Keywords:

Anesthesiology, Brain, Drugs Or Drug Abuse, Nervous System, Neurobiology, Neurons, Neurotransmitters, Pharmacology, Recombinant Dna.

Additional Terms:

Alcohol, Anesthesia, Drug Substance Abuse, Nervous System, Neurobiology, Neuroglia, Neurons, Peripheral Nervous System, Physiological Effects, Synapses, Transmitters.

Memberships

American Society for Cell Biology
American Society of Anesthesiologists
International Cannabinoid Research Society
Society for Neuroscience

Previous Positions

1992-1998, Assistant Professor, University of Washington, School of Medicine, Anesthesiology
1990-1992, Instructor, University of Washington
1990-1992, Senior Fellow, University of Washington
1987-1990, Resident, University of Washington, School of Medicine, Anesthesiology
1986-1987, Intern, Greenwich Hospital, Internal Medicine
1984-1986, Postdoctoral Fellow, Rockefeller University

Publications

  • Luk T, Jin W, Zvonok A, Lu D, Lin XZ, Chavkin C, Makriyannis A, Mackie K, Identification of a potent and highly efficacious, yet slowly desensitizing CB1 cannabinoid receptor agonist, British Journal of Pharmacology, 142(3), 495-500, 2004 Abstract
  • MacNaughton WK, Van Sickle MD, Keenan CM, Cushing K, Mackie K, Sharkey KA, Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves, American Journal of Physiology. Gastrointestinal and Liver Physiology, 286(5), G863-71, 2004 Abstract
  • Harkany T, Holmgren C, Hartig W, Qureshi T, Chaudhry FA, Storm-Mathisen J, Dobszay MB, Berghuis P, Schulte G, Sousa KM, Fremeau RT Jr, Edwards RH, Mackie K, Ernfors P, Zilberter Y, Endocannabinoid-independent retrograde signaling at inhibitory synapses in, The Journal of Neuroscience., 24(21), 4978-88, May 2004 Abstract
  • Harkany T, Hartig W, Berghuis P, Dobszay MB, Zilberter Y, Edwards RH, Mackie K, Ernfors P, Complementary distribution of type 1 cannabinoid receptors and vesicular glutamate transporter 3 in basal forebrain suggests input-specific retrograde signalling by cholinergic neurons, The European Journal of Neuroscience, 18(7), 1979-92, 2003 Abstract
  • McLaughlin JP, Xu M, Mackie K, Chavkin C, Phosphorylation of a carboxyl-terminal serine within the kappa-opioid receptor produces desensitization and internalization, Journal of Bioligical Chemistry, 278(36), 34631-40, 2003 Abstract
  • Van Sickle MD, Oland LD, Mackie K, Davison JS, Sharkey KA, Delta9-tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets, American Journal of Physiology. Gastrointestinal and Liver Physiology, 285(3), G566-76, 2003 Abstract
  • Chen K, Ratzliff A, Hilgenberg L, Gulyas A, Freund TF, Smith M, Dinh TP, Piomelli D, Mackie K, Soltesz I, Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures, Neuron, 39(4), 599-611, 2003 Abstract
  • Mackie K, Understanding marijuana: a new look at the scientific evidence, Nature Medicine, 9(3), 255, March 2003
  • Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N, Nonpsychotropic cannabinoid receptors regulate microglial cell migration, The Journal of Neuroscience., 23(4), 1398-405, February 2003 Abstract
  • Wager-Miller J, Westenbroek R, Mackie K, Dimerization of G protein-coupled receptors: CB1 cannabinoid receptors as an example, Chemistry and Physics of Lipids, 121(1-2), 83-9, December 2002
  • Roche JP, Westenbroek R, Sorom AJ, Hille B, Mackie K, Shapiro MS, Antibodies and a cysteine-modifying reagent show correspondence of M current in neurons to KCNQ2 and KCNQ3 K+ channels, British Journal of Pharmacology, 137(8), 1173-86, December 2002 Abstract
  • Van Sickle M, Davison J, Sharkey K, Mackie K, Hillard C, Reply, Gastroenterology, 123(2), 655-6, Aug 2002
  • Brown SM, Wager-Miller J, Mackie K, Cloning and molecular characterization of the rat CB2 cannabinoid receptor, Biochimica Et Biophysica Acta, 1576(3), 255-64, July 2002 Abstract
  • Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG, International Union of Pharmacology. XXVII. Classification of cannabinoid receptors, Pharmacological Reviews, 54(2), 161-202, June 2002 Abstract
  • Cesa R, Guastalla A, Cottone E, Mackie K, Beltramo M, Franzoni MF, Relationships between CB1 cannabinoid receptors and pituitary endocrine cells in Xenopus laevis: an immunohistochemical study, General and Comparative Endocrinology, 125(1), 17-24, January 2002 Abstract
  • Diana MA, Levenes C, Mackie K, Marty A, Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 22(1), 200-8, January 2002 Abstract
  • Katona I, Rancz EA, Acsady L, Ledent C, Mackie K, Hajos N, Freund TF, Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 21(23), 9506-18, December 2001 Abstract
  • Salio C, Fischer J, Franzoni MF, Mackie K, Kaneko T, Conrath M, CB1-cannabinoid and mu-opioid receptor co-localization on postsynaptic target in the rat dorsal horn, Neuroreport, 12(17), 3689-92, December 2001 Abstract
  • Cesa R, Mackie K, Beltramo M, Franzoni MF, Cannabinoid receptor CB1-like and glutamic acid decarboxylase-like immunoreactivities in the brain of Xenopus laevis, Cell and Tissue Research, 306(3), 391-8, December 2001 Abstract
  • Van Sickle MD, Oland LD, Ho W, Hillard CJ, Mackie K, Davison JS, Sharkey KA, Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret, Gastroenterology, 121(4), 767-74, October 2001 Abstract
  • Coutts AA, Anavi-Goffer S, Ross RA, MacEwan DJ, Mackie K, Pertwee RG, Irving AJ, Agonist-induced internalization and trafficking of cannabinoid CB1 receptors in hippocampal neurons, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 21(7), 2425-33, April 2001 Abstract
  • Rodriguez JJ, Mackie K, Pickel VM, Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat Caudate putamen nucleus, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 21(3), 823-33, February 2001 Abstract
  • Calignano A, Katona I, Desarnaud F, Giuffrida A, La Rana G, Mackie K, Freund TF, Piomelli D, Bidirectional control of airway responsiveness by endogenous cannabinoids, Nature, 408(6808), 96-101, November 2000 Abstract
  • Hajos N, Katona I, Naiem SS, MacKie K, Ledent C, Mody I, Freund TF, Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations, The European Journal of Neuroscience, 12(9), 3239-49, September 2000 Abstract
  • Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B, Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+\) channels that underlie the neuronal M current., Journal of Neuroscience, 20(5), 1710-21, 1 2000 Abstract
  • Sanudo-Pena MC, Tsou K, Romero J, Mackie K, Walker JM, Role of the superior colliculus in the motor effects of cannabinoids and dopamine, Brain Research, 853(2), 207-14, Jan 2000 Abstract
  • Irving AJ, Coutts AA, Harvey J, Rae MG, Mackie K, Bewick GS, Pertwee RG, Functional expression of cell surface cannabinoid CB(1) receptors on presynaptic inhibitory terminals in cultured rat hippocampal neurons, Neuroscience, 98(2), 253-62, 2000 Abstract
  • Katona I, Sperlagh B, Magloczky Z, Santha E, Kofalvi A, Czirjak S, Mackie K, Vizi ES, Freund TF, GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus, Neuroscience, 100(4), 797-804, 2000 Abstract
  • Roche JP, Bounds S, Brown S, Mackie K, A mutation in the second transmembrane region of the CB1 receptor selectively disrupts G protein signaling and prevents receptor internalization, Molecular Pharmacology, 56(3), 611-8, September 1999 Abstract
  • Straiker AJ, Maguire G, Mackie K, Lindsey J, Localization of cannabinoid CB1 receptors in the human anterior eye and retina, Investigative Ophthalmology and Visual Science, 40(10), 2442-8, September 1999 Abstract
  • Hsieh C, Brown S, Derleth C, Mackie K, Internalization and recycling of the CB1 cannabinoid receptor, Journal of Neurochemistry, 73(2), 493-501, August 1999 Abstract
  • Katona I, Sperlagh B, Sik A, Kafalvi A, Vizi ES, Mackie K, Freund TF, Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons, Journal of Neuroscience, 19(11), 4544-58, June 1999 Abstract
  • Jin W, Brown S, Roche JP, Hsieh C, Celver JP, Kovoor A, Chavkin C, Mackie K, Distinct domains of the CB1 cannabinoid receptor mediate desensitization and internalization, Journal of Neuroscience, 19(10), 3773-80, May 1999 Abstract
  • Ong WY, Mackie K, A light and electron microscopic study of the CB1 cannabinoid receptor in primate brain, Neuroscience, 92(4), 1177-91, 1999 Abstract
  • Tsou K, Mackie K, Sanudo-Pena MC, Walker JM, Cannabinoid CB1 receptors are localized primarily on cholecystokinin-containing GABAergic interneurons in the rat hippocampal formation, Neuroscience, 93(3), 969-75, 1999 Abstract
  • Garcia DE, Li B, Garcia-Ferreiro RE, Hernandez-Ochoa EO, Yan K, Gautam N, Catterall WA, Mackie K, Hille B, G-protein beta-subunit specificity in the fast membrane-delimited inhibition of Ca2 channels, Journal of Neuroscience, 18(22), 9163-70, November 1998 Abstract
  • Garcia D E, Brown S, Hille B, Mackie K, Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1 cannabinoid receptor, Journal of Neuroscience, 18(8), 2834-41, 15 Apr 1998 Abstract
  • Tsou K, Brown S, Sanudo-Pena M C, Mackie K, Walker J M, Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system, Neuroscience, 83(2), 393-411, March 1998 Abstract
  • Felder C C, Joyce K E, Briley E M, Glass M, Mackie K P, Fahey K J, Cullinan G J, Hunden D C, Johnson D W, Chaney M O, Koppel G A, Brownstein M, LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation, Journal of Pharmacology and Experimental Therapeutics, 284(1), 291-7, Jan 1998 Abstract
  • Twitchell W, Brown S, Mackie K, Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons, Journal of Neurophysiology, 78(1), 43-50, July 1997 Abstract
  • Twitchell W, Brown S, Mackie K, Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons., Journal of Neurophysiology, 78(1), 43-50, 1997 Abstract
  • Herlitze S, Garcia D E, Mackie K, Hille B, Scheuer T, Catterall W A, Modulation of Ca2+ channels by G-protein beta gamma subunits, Nature, 380(6571), 258-62, 21 Mar 1996 Abstract
  • Mackie K, Lai Y, Westenbroek R, Mitchell R, Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor, Journal of Neuroscience, 15(10), 6552-61, October 1995 Abstract
  • Felder C C, Joyce K E, Briley E M, Mansouri J, Mackie K, Blond O, Lai Y, Ma A L, Mitchell R L, Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors, Molecular Pharmacology, 48(3), 443-50, September 1995 Abstract
  • Priller J, Briley E M, Mansouri J, Devane W A, Mackie K, Felder C C, Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors, Molecular Pharmacology, 48(2), 288-92, August 1995 Abstract
  • Mackie K, Devane W A, Hille B, Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N18 neuroblastoma cells, Molecular Pharmacology, 44(3), 498-503, September 1993 Abstract
  • Felder C C, Briley E M, Axelrod J, Simpson J T, Mackie K, Devane W A, Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction, Proceedings of the National Academy of Sciences (USA), 90(16), 7656-60, 15 Aug 1993 Abstract
  • Mackie K, Hille B, Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells, Proceedings of the National Academy of Sciences (USA), 89(9), 3825-9, 1 May 1992 Abstract
  • Mackie K, Lam A, Epinephrine-containing test dose during beta-blockade, Journal of Clinical Monitoring, 7(3), 213-6, July 1991 Abstract
  • Mackie K, Pavlin E G, Recurrent paralysis following piperacillin administration, Anesthesiology, 72(3), 561-3, March 1990 Abstract
  • Mackie K, Sorkin BC, Nairn AC, Greengard P, Edelman GM, Cunningham BA, Identification of two protein kinases that phosphorylate the neural cell-adhesion molecule, N-CAM, Journal of Neuroscience, 9(6), 1883-96, June 1989 Abstract
  • Mackie KP, Nairn AC, Hampel G, Lam G, Jaffe EA, Thrombin and histamine stimulate the phosphorylation of elongation factor 2 in human umbilical vein endothelial cells, Journal of Biological Chemistry, 264(3), 1748-53, January 1989 Abstract
  • Mackie K, DePasquale M, Cserr HF, Increased permeability of a glial blood-brain barrier during acute hyperosmotic stress, American Journal of Physiology, 251(6 Pt 2), R1186-92, December 1986 Abstract
  • Mackie K, Lai Y, Nairn AC, Greengard P, Pitt BR, Lazo JS, Protein phosphorylation in cultured endothelial cells, Journal of Cellular Physiology, 128(3), 367-74, September 1986 Abstract

Profile Details

Last Updated: 7/15/2004

COS Expertise ID #403684
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