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Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones

  • SHIH-FANG FAN (a1) and STEPHEN YAZULLA (a1)

Abstract

Dopamine is a light-adaptive signal that desensitizes the retina, while cannabinoids reportedly increase photosensitivity. The presynaptic membrane of goldfish retinal cones has dopamine D2 receptors and cannabinoid CB1 receptors. This work focused on whether dopamine D2 receptor agonist quinpirole and cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) interacted to modulate voltage-dependent membrane currents of cones. A conventional patch-clamp method was used to record depolarization evoked whole-cell outward currents (Iout) and an inward calcium current (ICa) from the inner segment of cones in goldfish retinal slices. WIN had biphasic actions: low concentrations (<1 μM) increased the currents via Gs, while higher concentrations (>1 μM) decreased the currents via Gi/Go. Neither dopamine nor the D2 agonist quinpirole (1–20 μM) had a significant effect on either Iout or ICa. Quinpirole at 50 μM had a mild suppressive (∼20%) effect on Iout. However, quinpirole (<10 μM) completely blocked the enhancement of both currents seen with 0.7 μM WIN. The effect of quinpirole was blocked by sulpiride and by pertussis toxin, indicating that quinpirole was acting via a D2 receptor-Gi/o coupled mechanism. The suppressive action of 50 μM quinpirole (∼20%) was not additive with the suppressive effect of 3 μM WIN (∼40%). D2 agonists via Gi/o oppose the action of low concentrations of CB1 agonists acting via Gs to modulate cone membrane currents, suggesting a role in shaping the cone light response and/or sensitivity to changes in ambient light conditions. The nonadditive effect of high concentrations of WIN and quinpirole suggests that both decrease membrane currents via the same transduction pathway, Gi/Go protein kinase A (PKA).

Copyright

Corresponding author

Address correspondence and reprint requests to: Stephen Yazulla, Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794-5230, USA. E-mail: Stephen.Yazulla@stonybrook.edu

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REFERENCES

Akopian, A. & Witkovsky, P. (1996). D2 dopamine receptor-mediated inhibition of a hyperpolarization-activated current in rod photoreceptors. Journal of Neurophysiology 76, 18281835.
Akopian, A., Johnson, J., Gabriel, R., Brecha, N., & Witkovsky, P. (2000). Somatostatin modulates voltage-gated K+ and Ca2+ currents in rod and cone photoreceptors of the salamander retina. Journal of Neuroscience 20, 929936.
Barnes, S. & Hille, B. (1989). Ionic channels of the inner segment of tiger salamander cone photoreceptors. Journal of General Physiology 94, 719743.
Barnes, S. & Bui, Q. (1991). Modulation of calcium-activated chloride current via pH-induced changes of calcium channel properties in cone photoreceptors. Journal of Neuroscience 11, 40154023.
Barnes, S., Merchant, V., & Mahmud, F. (1993). Modulation of transmission gain by protons at the photoreceptor output synapse. Proceedings of the National Academy of Sciences of the U.S.A. 90, 1008110085.
Bodis-Wollner, I. & Antal, A. (1995). On the functional significance of primate retinal dopamine receptors. Journal of Neural Transmission 102, 6774.
Bodis-Wollner, I. & Tzelepi, A. (1998). The push–pull action of dopamine on spatial tuning of the monkey retina: The effects of dopaminergic deficiency and selective D1 and D2 receptor ligands on the pattern electroretinogram. Vision Research 38, 14791487.
Bonhaus, D.W., Chang, L.K., Kwan, J., & Martin, G.R. (1998). Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: Evidence for agonist-specific trafficking of intracellular responses. Journal of Pharmacology and Experimental Therapeutics 287, 884888.
Calandra, B., Porta, G., Kerim, S., Delpech, M., Carillon, C., Lazennec, C., Ferrara, P., & Shiono, H. (1999). Dual intracellular signaling pathways mediated by the human cannabinoid CB1 receptor. European Journal of Pharmacology 374, 445455.
Childers, S.R., Fleming, L., Konkoy, C., Marckel, D., Racheco, M., Sexton, T., & Ward, S. (1992). Opiod and cannabinoid receptor inhibition of adenylyl cyclase in brain. Annals of the New York Academy of Sciences 654, 3351.
Consroe, P., Musty, R., Rein, J., Tillery, W., & Pertwee, R.G. (1997). The perceived effects of smoked cannabis on patients with multiple sclerosis. European Neurology 38, 4448.
Dawson, W.W., Jimenez-Antillon, C.F., Perez, J.M., & Zeskind, J.A. (1977). Marijuana and vision—after ten years' use in Costa Rica. Investigative Ophthalmology and Visual Science 16, 689699.
Dearry, A. & Burnside, B. (1986). Dopaminergic regulation of cone retinomotor movement in isolated teleost retinas: I. Induction of cone contraction is mediated by D2 receptors. Journal of Neurochemistry 46, 10061021.
Devane, W.A., Spain, J.W., Coscia, C.J., & Howlett, A.C. (1986). An assessment of the role of opiod receptors in the response to cannabimimetic drugs. Journal of Neurochemistry 46, 19291935.
DeVries, S.H. (2001). Exocytosed protons feedback to suppress the Ca2+ current in mammalian cone photoreceptors. Neuron 32, 11071117.
Ellis, C.J.K., Allen, T.G., Marsden, C.D., & Ikeda, H. (1987). Electroretinographic abnormalities in idiopathic Parkinson's disease and the effect of levadopa administration. Clinical Vision Research 1, 347355.
Fan, S.F. & Yazulla, S. (1999a). Suppression of voltage-dependent K+ currents in retinal bipolar cells by ascorbate. Visual Neuroscience 16, 141148.
Fan, S.F. & Yazulla, S. (1999b). Modulation of voltage-gated K+ currents (IK(V)) in retinal bipolar cells by ascorbate is mediated by dopamine D1 receptors. Visual Neuroscience 16, 928931.
Fan, S.F. & Yazulla, S. (2003). Biphasic modulation of voltage-dependent currents of retinal cones by cannabinoid CB1 agonist, WIN 55212-2. Visual Neuroscience 20, 177188.
Fenwick, W.M., Marty, A., & Neher, E. (1982). A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. Journal of Physiology 331, 577597.
Gelmi, C., Sandrini, G., Martignoni, E., Bruno, A., Mappi, G., & Trimarchi, F. (1992). Electroretinograms and visual evoked potentials in Parkinsonian patients with or without L-Dopa treatment. Neuropharmacology 12, 125132.
Glaser, S.T., Studholme, K.M., Fatade, R., Yazulla, S., Abumrad, N.A., & Deutsch, D.G. (2002). Is there an anandamide transporter. 2002 Symposium on the Cannabinoids. Burlington, Vermont: International Cannabinoid Research Society.
Glass, M. & Felder, C.C. (1997). Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: Evidence for a Gs linkage to the CB1 receptor. Journal of Neuroscience 17, 53275333.
Gottlob, I., Strenn, K., & Schneider, B.G. (1994). Effect of levadopa on the human dark adaptation threshold. Graefes Archive for Clinical and Experimental Ophthalmology 232, 584588.
Hamil, O.P., Marty, A., Neher, E., Sakmann, B., & Sigworth, F.J. (1981). Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pflugers Archives 391, 85100.
Hampson, R.E., Mu, J.A., & Deadwyler, S.A. (2000). Cannabinoid and kappa opioid receptors reduce potassium K current via activation of G(S) proteins in cultured hippocampal neurons. Journal of Neurophysiology 84, 23562364.
Harnois, C. & Di Paolo, T. (1990). Decreased dopamine in the retinas of patients with Parkinson's disease. Investigative Ophthalmology and Visual Science 31, 24732475.
Harsanyi, K. & Mangel, S.C. (1992). Activation of a D 2 receptor increases electrical coupling between retinal horizontal cells by inhibiting dopamine release. Proceedings of the National Academy of Sciences of the U.S.A. 89, 92209224.
Hermann, H., Marsicano, G., & Lutz, B. (2002). Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 109, 451460.
Iuvone, P.M. (1986). Evidence for D2 dopamine receptor in frog retina that decreases cyclic AMP accumulation and serotonin N-acetyltransferase activity. Life Science 38, 331342.
Kamermans, M., Fahrenfort, I., & Sjoerdsma, T. (2002). GABAergic modulation of ephaptic feedback in the outer retina. Investigative Ophthalmology and Visual Science 43, E-Abstract 2920.
Kiplinger, G.F., Manno, J.E., Rodda, B.E., & Forney, R.B. (1971). Dose–response analysis of the effects of tetrahydrocannabinol in man. Clinical Pharmacology and Therapeutics 12, 650657.
Ko, G.Y., Ko, M.L., & Dryer, S.E. (2001). Circadian regulation of cGMP-gated cationic channels of chick retinal cones. Erk MAP Kinase and Ca2+/calmodulin-dependent protein kinase II. Neuron 29, 255266.
Ko, G.Y.P., Ko, M.L., & Dryer, S.E. (2003). Circadian phase-dependent modulation of cGMP-gated channels of cone photoreceptors by dopamine and D2 agonist. Journal of Neuroscience 23, 31453153.
Li, L. & Dowling, J.E. (2000). Effects of dopamine depletion on visual sensitivity of zebrafish. Journal of Neuroscience 20, 18931903.
Lin, Z.S. & Yazulla, S. (1994a). Depletion of retinal dopamine increases brightness perception in goldfish. Visual Neuroscience 11, 683693.
Lin, Z.S. & Yazulla, S. (1994b). Depletion of retinal dopamine does not affect the ERG b-wave increment threshold function in goldfish in vivo. Visual Neuroscience 11, 695702.
Liu, Y., Luo, F.J., & Liang, P.J. (2003). Dopamine effect on the stimulus pattern related changes in response characteristics of R/G horizontal cells in carp retina. Brain Research 973, 190195.
Maneuf, Y.P. & Brotchie, J.M. (1997). Paradoxical action of the cannabinoid WIN 55,212-2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices. British Journal of Pharmacology 120, 13971398.
Mangel, S.C. & Dowling, J.E. (1985). Responsiveness and receptive field size of carp horizontal cells are reduced by prolonged darkness and dopamine. Science 229, 11071109.
Mangel, S.C., Baldridge, W.H., Weiler, R., & Dowling, J.E. (1994). Threshold and chromatic sensitivity changes in fish cone horizontal cells following prolonged darkness. Brain Research 659, 5561.
McCormack, C.A. & McDonnell, M.T. (1994a). Circadian regulation of teleost retinal cone movements in vitro. Journal of General Physiology 103, 487499.
McCormack, C.A. & McDonnell, M.T. (1994b). Abnormal dorsal light response in teleost fish after intraocular injection of 6-hydroxydopamine. Journal of Fish Biology 45, 515525.
Meschler, J.P. & Howlett, A.C. (2001). Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum. Neuropharmacology 40, 918926.
Mukhopadhyay, S., Shim, J.Y., Assi, A.A., Norford, D., & Howlett, A.C. (2002). CB1 cannabinoid receptor-G protein association: A possible mechanism for differential signaling. Chemistry and Physics of Lipids 121, 91109.
Muller, T., Woitalla, D., Peters, S., Kohla, K., & Przuntek, H. (2002). Progressive visual dysfunction in Parkinson's disease. Acta Neurologica Scandinavica 105, 256260.
Nguyen-Legros, J., Harnois, C., Di Paolo, T., & Simon, A. (1993). The retinal dopamine system in Parkinson's disease. Clinical Visual Science 8, 112.
Parther, P.L., Martin, N.A., Breivogel, C.S., & Childers, S.R. (2000). Activation of cannabinoid receptors in rat brain by WIN 55212-2 produces coupling to multile G protein alpha-subunits with different potencies. Molecular Pharmacology 57, 10001010.
Piccolino, M., Byzov, A.L., Kurennyi, D.E., Pignatelli, A., Sappia, F., Wilkinson, M., & Barnes, S. (1996). Low-calcium-induced enhancement of chemical synaptic transmission from photoreceptors to horizontal cells in the vertebrate retina. Proceedings of the National Academy of Sciences of the U.S.A. 93, 23022306.
Picones, A. & Korenbrot, J.I. (1992). Permeation and interaction of monovalent cations with the cGMP-gated channel of cone photoreceptors. Journal of General Physiology 100, 647673.
Reese, K.M. (1991). Cannabis seems to improve night vision of fisherman. Chemical Engineering News 69, 44.
Ribelayga, C., Wang, Y., & Mangel, S.C. (2002). Dopamine mediates circadian clock regulation of rod and cone input to fish retinal horizontal cells. Journal of Physiology (London) 544, 801816.
Rieke, F. & Schwartz, E.A. (1994). A cGMP-gated current can control exocytosis at cone synapses. Neuron 13, 863873.
Savchenko, A., Barnes, S., & Kramer, R.H. (1997). Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide. Nature 390, 694698.
Schmitz, F., Kirsch, M., & Wagner, H.-J. (1989). Calcium modulated synaptic ribbon dynamics in cone photoreceptors: A pharmacological and electron spectroscopic study. European Journal of Cell Biology 49, 207212.
Shapira, M., Gafni, M., & Sarne, Y. (1998). Independence of, and interactions between, cannabinoid and opioid signal transduction pathways in N18TG2 cells. Brain Research 806, 2635.
Stanzione, P., Pierelli, F., Peppe, A., Stefani, E., Rizzo, P.A., Morocutti, C., & Bernardi, G. (1989). Pattern visual evoked potentials and electroretinogram abnormalities in Parkinson's disease—effects of L-DOPA therapy. Clinical Vision Research 4, 115127.
Stella, S.L. & Thoreson, W.B. (2000). Differential modulation of rod and cone calcium currents in tiger salamander retina by D2 dopamine receptors and cAMP. European Journal of Neuroscience 12, 35373548.
Stella, S.L., Bryson, E.J., & Thoreson, W.B. (2001). Insulin inhibits voltage-dependent calcium influx into rod photoreceptors. Neuroreport 12, 947951.
Stella, S.L., Bryson, E.J., & Thoreson, W.B. (2002). A(2) adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina. Journal of Neurophysiology 87, 351360.
Straiker, A., Stella, N., Piomelli, D., Mackie, K., Karten, H.J., & Maguire, G. (1999). Cannabinoid CB1 receptors and ligands in vertebrate retina: Localization and function of an endogenous signaling system. Proceedings of the National Academy of Sciences of the U.S.A. 96, 1456514570.
Straiker, A. & Sullivan, J.M. (2003). Cannabinoid receptor activation differentially modulates ion channels in photoreceptors of the tiger salamander. Journal of Neurophysiology 89, 26472654.
Tagliati, M., Bodis-Wollner, I., & Yahr, M.D. (1996). The pattern electroretinogram in Parkinson's disease reveals lack of retinal spatial tuning. Electroencephalography and Clinical Neurophysiology: Evoked Potentials 100, 111.
Thoreson, W.B. (2000). Dihydropyridine-sensitive calcium currents in bipolar cells of salamander retina are inhibited by reductions in extracellular chloride. Neuroscience Letters 280, 155158.
Thoreson, W.B., Nitzan, R., & Miller, R.F. (1997). Reducing extracellular Cl suppresses dihydropyridine-sensitive Ca2+ currents and synaptic transmission in amphibian photoreceptors. Journal of Neurophysiology 77, 21752190.
Vásquez, C. & Lewis, D.L. (1999). The CB1 cannabinoid receptor can sequester G proteins, making them unavailable to couple to other receptors. Journal of Neuroscience 19, 92719280.
Vellani, V., Reynolds, A.M., & McNaughton, P.A. (2000). Modulation of the synaptic Ca2+ current in salamander photoreceptors by polyunsaturated fatty acids and retinoids. Journal of Physiology (London) 529, 333344.
Verweij, J., Kamermans, M., & Spekreijse, H. (1996). Horizontal cells feed back to cones by shifting the cone calcium-current activation range. Vision Research 36, 39433953.
Wagner, H.-J. (1973). Darkness-induced reduction of the number of synaptic ribbons in fish retina. Nature New Biology 246, 5355.
Wagner, H.-J. & Ali, M.A. (1977). Cone synaptic ribbons and retinomotor changes in the brook trout, Salvelinus fontinalis (Salmonidae, Teleostei), under various experimental conditions. Canadian Journal of Zoology 55, 16841691.
Wagner, H.-J. & Behrens, U.D. (1993). Microanatomy of the dopaminergic system in the rainbow trout retina. Vision Research 33, 13451358.
Wang, Y. & Mangel, S.C. (1996). A circadian clock regulates rod and cone input to fish retinal cone horizontal cells. Proceedings of the National Academy of Sciences of the U.S.A. 93, 46554660.
Wang, Y., Harsanyi, K., & Mangel, S.C. (1997). Endogenous activation of dopamine D2 receptors regulates dopamine release in the fish retina. Journal of Neurophysiology 78, 439449.
West, M.E. (1991). Cannabis and night vision. Nature 351, 703704.
Witkovsky, P. & Dearry, A. (1992). Functional roles of dopamine in the vertebrate retina. Progress in Retinal Research 11, 113147.
Yazulla, S. (1985). Evoked efflux of 3H-GABA from goldfish retina in the dark. Brain Research 325, 171180.
Yazulla, S. & Lin, Z.-S. (1995). Differential effects of dopamine depletion on the distribution of 3H-SCH23390 and 3H-spiperone binding sites in the goldfish retina. Vision Research 35, 25092514.
Yazulla, S. & Studholme, K.M. (2001). Neurochemical anatomy of the zebrafish retina as determined by immunocytochemistry. Journal of Neurocytology 30, 551592.
Yazulla, S., Lin, Z.S., & Studholme, K.M. (1996). Dopaminergic control of light-adaptive synaptic plasticity and role in goldfish visual behavior. Vision Research 36, 40454057.
Yazulla, S., Studholme, K.M., McIntosh, H.H., & Fan, S.F. (2000). Cannabinoid receptors on goldfish retinal bipolar cells: Electron-microscope immunocytochemistry and whole-cell recordings. Visual Neuroscience 17, 391401.

Keywords

Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones

  • SHIH-FANG FAN (a1) and STEPHEN YAZULLA (a1)

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