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Retinal A2A and A3 adenosine receptors modulate the components of the rat electroretinogram

Published online by Cambridge University Press:  12 January 2017

GUDMUNDUR JONSSON  and
THOR EYSTEINSSON
GUDMUNDUR JONSSON
Affiliation:
Department of Physiology, University of Iceland, Reykjavik, Iceland
THOR EYSTEINSSON*
Affiliation:
Department of Physiology, University of Iceland, Reykjavik, Iceland
*
*Address correspondence to: Thor Eysteinsson, PhD, Department of Physiology, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland. E-mail: [email protected]
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Abstract

Adenosine is a neuromodulator present in various areas of the central nervous system, including the retina. Adenosine may serve a neuroprotective role in the retina, based on electroretinogram (ERG) recordings from the rat retina. Our purpose was to assess the role of A2A and A3 adenosine receptors in the generation and modulation of the rat ERG. The flash ERG was recorded with corneal electrodes from Sprague Dawley rats. Agonists and antagonists for A2A and A3 receptors, and adenosine were injected (5 µl) into the vitreous. The effects on the components of the single flash scotopic and photopic ERGs were examined, and ERG flicker. Adenosine (0.5 mM) increased the mean amplitudes of the scotopic ERG a-waves (68 ± 8 to 97 ± 14 µV, P = 0.042), and b-waves (236 ± 38 µV to 305 ± 42 µV). A2A agonist CGS21680 (2 mM) reduced the mean amplitude of the ERG b-wave, from 298 ± 21 µV in response to the brightest stimulus to 212 ± 19 µV (P = 0.005), and mean scotopic oscillatory potentials (OPs) from 100 ± 9 µV to 47 ± 11 µV (P = 0.023). ZM241385 [4 mM], an A2A antagonist, decreased the scotopic b-wave of the ERG. A3 agonist 2-CI-IB-MECA (0.5 mM) increased the a-wave, while decreasing the scotopic and photopic ERG b-waves, and the scotopic OPs. A3 antagonist VUF5574 (1 mM) increased the mean amplitude of the scotopic a-wave (66 ± 8 to 140 ± 29 µV, P = 0.046) and b-wave (224 ± 20 to 312 ± 39 µV, P = 0.0037). No significant effects on ERG flicker were found. We conclude that retinal neurons containing A2A and/or A3 adenosine receptors contribute to the generation of the ERG a- and b-waves and OPs.

Keywords

AdenosinePurine receptorsRetinaRatElectroretinogram
Type
Research Article
Information
Visual Neuroscience , Volume 34 , 2017 , E001
Copyright
Copyright © Cambridge University Press 2017 

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References

Awatramani, G., Wang, J. & Slaughter, M.M. (2001). Amacrine and ganglion cell contribution to the electroretinogram in amphibian retina. Visual Neuroscience 18, 147–156.Google Scholar
Blazynski, C. (1989). Displaced cholinergic, GABAergic amacrine cells in the rabbit retina also contain adenosine. Visual Neuroscience 3, 425–431.Google Scholar
Blazynski, C. (1990). Discrete distribution of adenosine receptors in the mammalian retina. Journal of Neurochemistry 54, 648–655.Google Scholar
Blazynski, C., Cohen, A.I., Fruh, B. & Niemeyer, G. (1989). Adenosine: Autoradiographic localization and electrophysiologic effects in the cat retina. Investigative Ophthalmology and Visual Science 30, 2533–2536.Google Scholar
Blazynski, C. & Perez, M.T.R. (1991). Adenosine in vertebrate retina: Locaization, receptor characterization, and function. Cellular and Molecular Biology 11, 463–484.Google Scholar
Brass, K.M., Zarbin, M.A. & Snyder, S.H. (1987). Endogenous adenosine and adenosine receptors localized to ganglion cells of the retina. Proceedings of the National Academy of Sciences 84, 3906–3910.Google Scholar
Bui, B.V. & Fortune, B. (2004). Ganglion cell contributions to the rat full-field electroretinogram. Journal of Physiology 555, 153–173.Google Scholar
Burnstock, G. (2007). Purine and pyrimidine receptors. Cellular and Molecular Life Sciences 64, 1471–1483.Google Scholar
Bush, R.A. & Sieving, P.A. (1994). A proximal retinal component in the primate photopic ERG a-wave. Investigative Ophthalmology and Visual Science 35, 635–645.Google Scholar
Ciruela, F., Albergaria, C., Soriano, A., Cuffí, L., Carbonell, L., Sánchez, S., Gandía, J. & Fernández-Dueñas, V. (2010). Adenosine receptors interacting proteins (ARIPs): Behind the biology of adenosine signaling. Biochimica et Biophysica Acta 1798, 9–20.Google Scholar
Clark, B.D., Kurth-Nelson, Z.L. & Newman, E.A. (2009). Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by G-protein-coupled inwardly rectifying K+ and small conductance Ca2+-activated K+ channel activation. Journal of Neuroscience 29, 11237–11245.Google Scholar
Costenla, A.R., De Mendonca, A., Sebastiao, A. & Ribeiro, J.A. (1999). An adenosine analogue inhibits NMDA-mediated responses in bipolar cells of the retina. Experimental Eye Research 68, 367–370.Google Scholar
Dang, T.M., Tsai, T.I., Vingrys, A.J. & Bui, B.V. (2011). Post-receptoral contributions to the rat scotopic electroretinogram a-wave. Documenta Ophthalmologica 122, 149–156.Google Scholar
Dunwiddie, T.V. & Masino, S.A. (2001). The role and regulation of adenosine in the central nervous system. Annual Review of Neuroscience 24, 31–55.Google Scholar
Dong, C.J. & Hare, W.A. (2002). GABAc feedback pathway modulates the amplitude and kinetics of ERG b-wave in a mammalian retina. Vision Research 42, 1081–1087.CrossRefGoogle Scholar
Fredholm, B.B., Izerman, A.P., Jacobson, K.A., Klotz, K.N. & Linden, J. (2001). International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacological Reviews 53, 527–552.Google Scholar
Fredholm, B.B. (2014). Adenosine—A physiological or pathophysiological agent? Journal of Molecular Medicine 92, 201–206.Google Scholar
Galvao, J., Elvas, F., Martins, T., Cordeiro, M.F., Ambrósio, A.F. & Santiago, A.R. (2015). Adenosine A3 receptor activation is neuroprotective against retinal neurodegeneration. Experimental Eye Research 140, 65–74.Google Scholar
Gao, Z.G., Blaustein, J.B., Gross, A.S., Melman, N. & Jacobson, K.A. (2003). N6-substituted adenosine derivatives: Selectivity, efficacy, and species differences at A3 adenosine receptors. Biochemical Pharmacology 65, 1675–1684.Google Scholar
Goto, Y. (1996). An electrode to record the mouse electroretinogram. Documenta Ophthalmologica 91, 147–154.Google Scholar
Hartwick, A.T.E., Lalonde, M.R., Barnes, S. & Baldridge, W.H. (2004). Adenosine A1 receptor modulation of glutamate-induced calcium influx in rat retinal ganglion cells. Investigative Ophthalmology and Visual Science 45, 3740–3748.CrossRefGoogle ScholarPubMed
Huang, P.C., Hsiao, Y.T., Kao, S.Y., Chen, C.F., Chen, C.F., Chiang, C.W., Lee, C.F., Lu, J.C., Chern, J. & Wang, C.T. (2014). Adenosine A2A receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. PloS ONE 9, e95090.Google Scholar
Jacobson, K.A. (1998). Adenosine A3 receptors: Novel ligands and paradoxical effects. Trends in Pharmacological Sciences 19, 184–191.Google Scholar
Jacobson, K.A. & Gao, Z.G. (2006). Adenosine receptors as therapeutic targets. Nature Reviews Drug Discovery 5, 247–264.Google Scholar
Kaelin-Lang, A., Jurklies, B. & Niemeyer, G. (1999). Effects of adenosinergic agents on the vascular resistance and on the optic nerve response in the perfused cat eye. Vision Research 39, 1059–1068.Google Scholar
Kvanta, A., Seregard, S., Sejersen, S., Kull, B. & Fredholm, B.B. (1997). Localization of adenosine messenger RNAs in the rat eye. Experimental Eye Research 65, 595–602.Google Scholar
Lassila, J.K., Zalatan, J.G. & Herschlag, D. (2011). Biological phosphoryl-transfer reactions: Understanding mechanism and catalysis. Annual Review of Biochemistry 80, 669–702.CrossRefGoogle ScholarPubMed
Li, B. & Roth, S. (1999). Retinal ischemic preconditioning in the rat: Requirement for adenosine and repetitive induction. Investigative Ophthalmology and Visual Science 40, 1200–1216.Google ScholarPubMed
Macaluso, C., Frishman, L.J., Frueh, B., Kaeling-Lang, A., Onoe, S. & Niemeyer, G. (2003). Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina. Documenta Ophthalmologica 106, 51–59.Google Scholar
McIntosh, H.H. & Blazynski, C. (1994). Characterization and localization of adenosine A2 receptors in bovine rod outer segments. Journal of Neurochemistry 62, 992–997.Google Scholar
Muller, C.E. & Jacobson, K.A. (2011). Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochimica et Biophysica Acta 1808, 1290–1308.Google Scholar
Mojumder, D.K., Sherry, D.M. & Frishman, L.J. (2008). Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram. Journal of Physiology 586, 2551–2580.Google Scholar
Möller, A. & Eysteinsson, T. (2003). Modulation of the components of the rat dark-adapted electroretinogram by the three subtypes of GABA receptors. Visual Neuroscience 20, 535–542.Google Scholar
Olah, M.E. & Stiles, G.L. (2000). The role of receptor structure in determining adenosine receptor activity. Pharmacology and Therapeutics 85, 55–75.Google Scholar
Paes de Carvalho, R., Braas, K.M., Snyder, S.H. & Adler, R. (1990). Analysis of adenosine immunoreactivity, uptake, and release in purified cultures of developing chick embryo retinal neurons and photoreceptors. Journal of Neurochemistry 55, 1601–1611.Google Scholar
Popova, E. & Kupenova, P. (2009). Contribution of proximal retinal neurons to b- and d-waves of frog electroretinogram under different conditions of light adaptation. Vision Research 49, 2001–2010.Google Scholar
Poucher, S., Keddie, J., Singh, P., Stoggall, S., Caulkett, P., Jones, G. & Coll, M. (1995). The in vitro pharmacology of ZM241385, a potent, non-xanthine A2a selective adenosine receptor antagonist. British Journal of Pharmacology 115, 1096–1102.Google Scholar
Quarta, D., Ferre, S., Solinas, M., You, Z.B., Hockemeyer, J., Popoli, P. & Goldberg, S.R. (2004). Opposite modulatory roles for adenosine A1 and A2A receptors on glutamate and dopamine release in the shell of the nucleus accumbens. Effects of chronic caffeine exposure. Journal of Neurochemistry 88, 1151–1158.Google Scholar
Ralevic, V. & Burnstock, G. (1998). Receptors for purines and pyrimidines. Pharmacological Reviews 50, 413–492.Google ScholarPubMed
Rey, H.L. & Burnside, B. (1999). Adenosine stimulates cone photoreceptor myoid elongation via an adenosine A2-like receptor. Journal of Neurochemistry 72, 2345–2355.Google Scholar
Ribelayga, C. & Mangel, S.C. (2005). A circadian clock and light/dark adaptation differentially regulate adenosine in the mammalian retina. Journal of Neuroscience 25, 215–222.Google Scholar
Ribeiro, J.A., Sebastiao, A.M. & de Mendonca, A. (2003). Adenosine receptors in the nervous system: Pathophysiological implications. Progress in Neurobiology 68, 377–392.Google Scholar
Ribeiro, J.A. & Sebastiao, A.M. (2010). Modulation and metamodulation of synapses by adenosine. Acta Physiologica 199, 161–169.Google Scholar
Ridder, W.H., Nusinowitz, S. & Heckenlively, J.R. (2002). Causes of cataract development in anaesthetized mice. Experimental Eye Research 75, 365–370.Google Scholar
Robson, J.G. & Frishman, L.J. (1998). Dissecting the dark-adapted electroretinogram. Documenta Ophthalmologica 95, 187–215.CrossRefGoogle ScholarPubMed
Robson, J.G., Saszik, S.M., Ahmed, J. & Frishman, L.J. (2003). Rod and cone contributions to the a-wave of the electroretinogram of the macaque. Journal of Physiology 547, 509–530.Google Scholar
Robson, J.G. & Frishman, L.J. (2014). The rod-driven a-wave of the dark-adapted mammalian electroretinogram. Progress in Retinal and Eye Research 39, 1–22.Google Scholar
Roth, S. (2004). Endogenous neuroprotection in the retina. Brain Research Bulletin 62, 461–466.Google Scholar
Rudolphi, K.A., Schubert, P., Parkinson, F.E. & Fredholm, B.B. (1992). Neuroprotective role of adenosine in cerebral ischaemia. Trends in Pharmacological Sciences 13, 439–445.Google Scholar
Sebastiao, A.M. & Ribeiro, J.A. (2009). Tuning and fine-tuning of synapses with adenosine. Current Neuropharmacology 7, 180–194.Google Scholar
Serrato, A., Tzekov, R. & Marmor, M.F. (2003). The lens-coating agent and the electroretinogram. Documenta Ophthalmologica 106, 225–230.Google Scholar
Sodhi, P. & Hartwick, A.T.E. (2014). Adenosine modulates light responses of rat retinal ganglion cell photoreceptors through a cAMP-mediated pathway. Journal of Physiology 592, 4201–4220.Google Scholar
Smith, B.J., Tremblay, F. & Cote, P.D. (2013). Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell GABAc receptors. Experimental Eye Research 116, 279–290.Google Scholar
Stella, S.L., Bryson, E.J. & Thoreson, W.B. (2002). A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina. Journal of Neurophysiology 87, 351–360.Google Scholar
Stella, S.L., Bryson, E.J., Cadetti, L. & Thoreson, W.B. (2003). Endogenous adenosine reduces glutamatergic output from rods through activation of A2-like adenosine receptors. Journal of Neurophysiology 90, 165–174.Google Scholar
Stella, S.L., Hu, W.D., Vila, A. & Brecha, N.C. (2007). Adenosine inhibits voltage-dependent Ca2+-influx in cone photoreceptor terminals of the tiger salamander retina. Journal of Neuroscience Research 85, 1126–1137.Google Scholar
Stella, S.L., Hu, W.D. & Brecha, N.C. (2009). Adenosine suppresses exocytosis from cone terminals of the salamander retina. NeuroReport 20, 923–929.Google Scholar
Stockton, R.A. & Slaughter, M.M. (1989). B-wave of the electroretinogram: A reflection of on-bipolar cell activity. Journal of General Physiology 93, 101–122.CrossRefGoogle ScholarPubMed
Stone, T.W., Ceruti, S. & Abbracchio, M.P. (2009). Adenosine receptors and neurological disease: Neuroprotection and neurodegeneration. Handbook of Experimental Pharmacology 193, 535–587.Google Scholar
Studholme, K.M. & Yazulla, S. (1997). 3H-adenosine uptake selectively labels rod horizontal cells in goldfish retina. Visual Neuroscience 14, 207–212.Google Scholar
Sun, X., Barnes, S. & Baldridge, W.H. (2002). Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation. Journal of Neurochemistry 81, 550–556.Google Scholar
van Muijlwijk-Koezen, J.E., Timmerman, H., van der Goot, H., Menge, W.M.P.B., Kunzel, J.F.D., de Groote, M. & Ijzerman, P. (2000). Isoquinoline and quinazoline urea analogues as antagonists for the human adenosine A3 receptor. Journal of Medicinal Chemistry 43, 2227–2238.Google Scholar
Wachtmeister, L. (1998). Oscillatory potentials in the retina: What do they reveal? Progress in Retinal and Eye Research 17, 485–521.Google Scholar
Wang, C., Blankenship, A.G., Anishchenko, A., Elstrott, J., Fikhman, M., Nakanishi, S. & Feller, M.B. (2007). GABAa receptor-mediated signaling alters the structure of spontaneous activity in the developing retina. Journal of Neuroscience 27, 9130–9140.Google Scholar
Zhang, C. & McCall, M.A. (2012). Receptor targets of amacrine cells. Visual Neuroscience 29, 11–29.Google Scholar
Zhang, X., Budak, M., Lu, W., Khurana, T., Zhang, X., Laties, A.M. & Mitchell, C.H. (2006). Identification of the A3 adenosine receptor in rat retinal ganglion cells. Molecular Vision 12, 937–948.Google Scholar
Zhang, M., Hu, H., Zhang, X., Lu, W., Lim, J., Eysteinsson, T., Jacobson, K.A., Laties, A.M. & Mitchell, C.H. (2010). The A3 adenosine receptor attenuates the calcium rise triggered by NMDA receptors in retinal ganglion cells. Neurochemistry International 56, 35–41.Google Scholar
Zhong, Y., Yang, Z., Huang, W.C. & Luo, X. (2013). Adenosine, adenosine receptors and glaucoma: An updated overview. Biochimica et Biophysica Acta 1830, 2882–2890.Google Scholar