Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-23T19:12:34.996Z Has data issue: false hasContentIssue false

Cannabinoid agonist WIN 55212-2 speeds up the cone response to light offset in goldfish retina

Published online by Cambridge University Press:  24 April 2006

MIEKE L. STRUIK
Affiliation:
The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands
STEPHEN YAZULLA
Affiliation:
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York
MAARTEN KAMERMANS
Affiliation:
The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands

Abstract

Goldfish cones contain CB1 receptors at the synaptic terminal, selectively accumulate 3H-anandamide, and contain fatty acid amide hydrolase-immunoreactivity, and voltage-gated calcium and potassium currents are modulated by CB1 ligands (Yazulla et al., 2000; Fan & Yazulla, 2003; Glaser et al., 2005). These data suggest that a retinal mechanism may account for some of the psychophysical effects of cannabis. Here, we studied the effect of a cannabinoid agonist on cone light responses. Whole-cell patch-clamp recordings were made from cones in the isolated goldfish retina. Cones were stimulated with a spot of light of variable wavelength and intensities in combination with voltage-and current-clamp protocols. Pharmacological manipulation was performed using the cannabinoid agonist WIN 55212-2 (10 μM). WIN had no effect on the absolute sensitivity of the cones or on the kinetics of the onset response. However, the light-offset response became faster, and the depolarizing overshoot was enhanced. Time constant of the offset response was reduced from 292 ± 28 ms to 180 ± 11 ms (n = 6) (P < 0.01) in the presence of WIN. Acceleration of the offset response was not affected by flash length from 200 ms to 10 s. This was found under current-clamp as well as under voltage-clamp conditions, indicating that the effect of WIN was mediated directly or indirectly by modulation of the cGMP-gated channels in the outer segment of the cones. The effects of WIN were not blocked by the CB1 antagonist SR141716A. With a train of “dark” flashes from a steady background, the photocurrent recovered toward baseline more quickly with WIN than in Control. In summary, cannabinoids speed up the dynamics of the phototransduction deactivation cascade in the cone outer segments. The functional consequence of this effect is to shorten the recovery time to the offset of bright flashes, perhaps resulting in an increase in contrast sensitivity.

Type
Research Article
Copyright
2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Adams, A.J., Brown, B., Haegerstrom-Portnoy, G., Flom, M.C., & Jones, R.T. (1978). Marijuana, alcohol, and combined drug effects on the time course of glare recovery. Psychopharmacology 56, 8186.CrossRefGoogle Scholar
Arshavsky, V.Y., Lamb, T.D., & Pugh, E.N., Jr. (2002). G proteins and phototransduction. Annual Review of Physiology 64, 153187.CrossRefGoogle Scholar
Baylor, D.A. & Hodgkin, A.L. (1974). Changes in time scale and sensitivity in turtle photoreceptors. Journal of Physiology (London) 242, 729753.CrossRefGoogle Scholar
Bisogno, T., Delton-Vandenbroucke, I., Milone, A., Lagarde, M., & Di Marzo, V. (1999). Biosynthesis and inactivation of N-arachidonoylethanolamine (anandamide) and Ndocosahexaenoylethanolamine in bovine retina. Archives of Biochemistry and Biophysics 370, 300307.CrossRefGoogle Scholar
Breivogel, C.S., Griffin, G., DiMarzo, V., & Martin, B.R. (2001). Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Molecular Pharmacology 60, 155163.Google Scholar
Buckley, N.E., Hansson, S., Harta, G., & Mezey, É. (1998). Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat. Neuroscience 82, 11311149.Google Scholar
Burkhardt, D.A. (1994). Light adaptation and photopigment bleaching in cone photoreceptors in situ in the retina of the turtle. Journal of Neuroscience 14, 10911105.Google Scholar
Chen, C.K., Burns, M.E., He, W., Wensel, T.G., Baylor, D.A., & Simon, M.I. (2000). Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature 403, 557560.CrossRefGoogle Scholar
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.Google Scholar
Cowan, C.W., Fariss, R.N., Sokal, I., Palczewski, K., & Wensel, T.G. (1998). High expression levels in cones of RGS9, the predominant GTPase accelerating protein of rods. Proceedings of the National Academy of Science of the U.S.A. 95, 53515356.CrossRefGoogle Scholar
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.Google Scholar
Devane, W.A., Dysarz, F.A.I., Johnson, M.R., Melvin, L.S., & Howlett, A.C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology 34, 605613.Google Scholar
Devane, W.A., Hanus, L., Breuer, A., Pertwee, R.G., Stevenson, L.S., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 19461949.CrossRefGoogle Scholar
Fain, G.L., Matthews, H.R., Cornwall, M.C., & Koutalos, Y. (2001). Adaptation in vertebrate photoreceptors. Physiological Reviews 81, 117151.Google Scholar
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.CrossRefGoogle Scholar
Fan, S.F. & Yazulla, S. (2004). Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones. Visual Neuroscience 21, 6979.CrossRefGoogle Scholar
Fan, S.F. & Yazulla, S. (2005). Reciprocal inhibition of voltage-gated potassium currents (I K(V)) by activation of cannabinoid CB1 and dopamine D1 receptors in ON bipolar cells of goldfish retina. Visual Neuroscience 22, 5563.CrossRefGoogle Scholar
Gaoni, Y. & Mechoulam, R. (1964). Isolation, structure and partial synthesis of an active constituent of hashish. Journal of the American Chemical Society 86, 16461647.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Hanus, L., Abu-Lafi, S., Fride, E., Breuer, A., Vogel, Z., Shalev, D.E., Kustanovich, I., & Mechoulam, R. (2001). 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proceedings of the National Academy of Sciences of the U.S.A. 98, 36623665.CrossRefGoogle Scholar
He, W., Cowan, C.W., & Wensel, T.G. (1998). RGS9, a GTPase accelerator for phototransduction. Neuron 20, 95102.CrossRefGoogle Scholar
Herkenham, M., Lynn, A.B., Ross Johnson, M.R., Melvin, L.S., de Costa, B.R., & Rice, K.C. (1991). Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. Journal of Neuroscience 11, 563583.Google Scholar
Howlett, A.C. & Fleming, R.M. (1984). Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Molecular Pharmacology 26, 532538.Google Scholar
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.CrossRefGoogle Scholar
Krispel, C.M., Chen, C.K., Simon, M.I., & Burns, M.E. (2003a). Novel form of adaptation in mouse retinal rods speeds recovery of phototransduction. Journal of General Physiology 122, 703712.Google Scholar
Krispel, C.M., Chen, C.K., Simon, M.I., & Burns, M.E. (2003b). Prolonged photoresponses and defective adaptation in rods of Gbeta5−/− mice. Journal of Neuroscience 23, 69656971.Google Scholar
Lyubarsky, A.L., Chen, C.K., Simon, M.I., & Pugh, E.N., Jr. (2000). Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses. Journal of Neuroscience 20, 22092217.Google Scholar
Lyubarsky, A.L., Naarendorp, F., Zhang, X., Wensel, T., Simon, M.I., & Pugh, E.N., Jr. (2001). RGS9-1 is required for normal inactivation of mouse cone phototransduction. Molecular Vision 7, 7178.Google Scholar
Makino, E.R., Handy, J.W., Li, T., & Arshavsky, V.Y. (1999). The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein beta subunit. Proceedings of the National Academy of Science of the U.S.A. 96, 19471952.CrossRefGoogle Scholar
Matsuda, L.A., Lolait, S.J., Brownstein, M.J., Young, A.C., & Bolnier, T.I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561564.CrossRefGoogle Scholar
Matsuda, S., Kanemitsu, N., Nakamura, A., Mimura, Y., Ueda, N., Kurahashi, Y., & Yamamoto, S. (1997). Metabolism of anandamide, an endogenous cannabinoid receptor ligand, in porcine ocular tissues. Experimental Eye Research 64, 707711.CrossRefGoogle Scholar
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumdky, M., Kaminski, N.E., Shatz, A.R., Gopher, A., Almog, S., Martin, B.R., & Compton, D.R. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemical Pharmacology 50, 8390.CrossRefGoogle Scholar
Pugh, E.N., Jr., Nikonov, S., & Lamb, T.D. (1999). Molecular mechanisms of vertebrate photoreceptor light adaptation. Current Opinion in Neurobiology 9, 410418.CrossRefGoogle Scholar
Reese, K.M. (1991). Cannabis seems to improve night vision of fishermen. Chemical Engineering News 69, 44.Google Scholar
Sagoo, M.S. & Lagnado, L. (1997). G-protein deactivation is rate-limiting for shut-off of the phototransduction cascade. Nature 389, 392395.Google Scholar
Savinainen, J.R. & Laitinen, J.T. (2004). Detection of cannabinoid CB1, adenosine A1, muscarinic acetylcholine, and GABA(B) receptor-dependent G protein activity in transducindeactivated membranes and autoradiography sections of rat retina. Cellular and Molecular Neurobiology 24, 243256.CrossRefGoogle Scholar
Schlicker, E., Timm, J., & Göthert, M. (1996). Cannabinoid receptor-mediated inhibition of dopamine release in the retina. Naunyn-Schmiedebergs Archives of Pharmacology 354, 791795.CrossRefGoogle Scholar
Stamer, W.D., Golightly, S.F., Hosohata, Y., Ryan, E.P., Porter, A.C., Varga, E., Noecker, R.J., Felder, C.C., & Yamamura, H.I. (2001). Cannabinoid CB(1) receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues. European Journal of Pharmacology 431, 277286.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Straiker, A. & Sullivan, J.M. (2003). Cannabinoid receptor activation differentially modulates ion channels in photoreceptors of the tiger salamander. Journal of Neurophysiology 89, 26472654.CrossRefGoogle Scholar
Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., & Waku, K. (1995). 2-Arachidonoylglycerol: A possible endogenous cannabinoid receptor ligand in brain. Biochemical and Biophysical Research Communications 215, 8997.CrossRefGoogle Scholar
Vuong, T.M. & Chabre, M. (1991). Deactivation kinetics of the transduction cascade of vision. Proceedings of the National Academy of Sciences of the U.S.A. 88, 98139817.CrossRefGoogle Scholar
Yazulla, S., Studholme, K.M., McIntosh, H.H., & Deutsch, D.G. (1999). Immunocytochemical localization of cannabinoid CB1 receptor and fatty acid amide hydrolase in rat retina. Journal of Comparative Neurology 415, 8090.3.0.CO;2-H>CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Zhao, X., Huang, J., Khani, S.C., & Palszewski, K. (1998). Molecular forms of human rhodopsin kinase (GRK1). Journal of Biological Chemistry 273, 51245131.CrossRefGoogle Scholar