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Abstract:

Dopamine is a retinal neuromodulator that has been implicated in many aspects of retinal physiology. Photoreceptor cells express dopamine D4 receptors that regulate cAMP metabolism. To assess the effects of dopamine on photoreceptor physiology, we examined the morphology, electrophysiology, and regulation of cAMP metabolism in mice with targeted disruption of the dopamine D4 receptor gene. Photoreceptor morphology and outer segment disc shedding after light onset were normal in D4 knock-out (D4KO) mice. Quinpirole, a dopamine D2/ D3/D4 receptor agonist, decreased cAMP synthesis in retinas of wild-type (WT) mice but not in retinas of D4KO mice. In WT retinas, the photoreceptors of which were functionally isolated by incubation in the presence of exogenous glutamate, light also suppressed cAMP synthesis. Despite the similar inhibition of cAMP synthesis, the effect of light is directly on the photo-receptors and independent of dopamine modulation, because it was unaffected by application of the D4 receptor antagonist L-745,870. Nevertheless, compared with WT retinas, basal cAMP formation was reduced in the photoreceptors of D4KO retinas, and light had no additional inhibitory effect. The results suggest that dopamine, via D4 receptors, normally modulates the cascade that couples light responses to adenylyl cyclase activity in photoreceptor cells, and the absence of this modulation results in dysfunction of the cascade. Dark-adapted electroretinogram (ERG) responses were normal in D4KO mice. However, ERG b-wave responses were greatly suppressed during both light adaptation and early stages of dark adaptation. Thus, the absence of D4 receptors affects adaptation, altering transmission of light responses from photoreceptors to inner retinal neurons. These findings indicate that dopamine D4 receptors normally play a major role in regulating photoreceptor cAMP metabolism and adaptive retinal responses to changing environmental illumination.

Registro:

Documento: Artículo
Título:Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors
Autor:Nir, I.; Harrison, J.M.; Haque, R.; Low, M.J.; Grandy, D.K.; Rubinstein, M.; Iuvone, P.M.
Filiación:Department of Pharmacology, Univ. TX Hlth. Sci. Ctr. San Antonio, San Antonio, TX 78229, United States
Department of Ophthalmology, Univ. TX Hlth. Sci. Ctr. San Antonio, San Antonio, TX 78229, United States
Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, United States
Vollum Institute, Oregon Health and Science University, Portland, OR 97201, United States
Department of Physiology, Oregon Health and Science University, Portland, OR 97201, United States
Inst. de Invest./Ingenieria Genetica, Department of Biological Science, University de Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:Adaptation; cAMP; Dopamine; Dopamine D4 receptors; Electroretinogram; Light adaptation; Photoreceptor; Retina; 3 [[4 (4 chlorophenyl) 1 piperazinyl]methyl] 1h pyrrolo[2,3 b]pyridine; cyclic AMP; dopamine; dopamine 4 receptor; quinpirole; animal experiment; animal tissue; article; B wave; controlled study; dark adaptation; electrophysiology; electroretinogram; enzyme activity; gene disruption; illumination; knockout mouse; light adaptation; mouse; neuromodulation; nonhuman; photoreactivity; photoreceptor; priority journal; retina; retina nerve cell; Adaptation, Ocular; Animals; Cell Survival; Cyclic AMP; Darkness; Dopamine; Dopamine Agonists; Glutamic Acid; Light; Mice; Mice, Inbred C57BL; Mice, Knockout; Phagocytosis; Photoreceptors, Vertebrate; Quinpirole; Receptors, Dopamine D2; Receptors, Dopamine D4; Retina; Rod Outer Segments
Año:2002
Volumen:22
Número:6
Página de inicio:2063
Página de fin:2073
Título revista:Journal of Neuroscience
Título revista abreviado:J. Neurosci.
ISSN:02706474
CODEN:JNRSD
CAS:Cyclic AMP, 60-92-4; Dopamine Agonists; Dopamine, 51-61-6; Drd4 protein, mouse; Glutamic Acid, 56-86-0; Quinpirole, 85760-74-3; Receptors, Dopamine D2; Receptors, Dopamine D4, 137750-34-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v22_n6_p2063_Nir

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Citas:

---------- APA ----------
Nir, I., Harrison, J.M., Haque, R., Low, M.J., Grandy, D.K., Rubinstein, M. & Iuvone, P.M. (2002) . Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. Journal of Neuroscience, 22(6), 2063-2073.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v22_n6_p2063_Nir [ ]
---------- CHICAGO ----------
Nir, I., Harrison, J.M., Haque, R., Low, M.J., Grandy, D.K., Rubinstein, M., et al. "Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors" . Journal of Neuroscience 22, no. 6 (2002) : 2063-2073.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v22_n6_p2063_Nir [ ]
---------- MLA ----------
Nir, I., Harrison, J.M., Haque, R., Low, M.J., Grandy, D.K., Rubinstein, M., et al. "Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors" . Journal of Neuroscience, vol. 22, no. 6, 2002, pp. 2063-2073.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v22_n6_p2063_Nir [ ]
---------- VANCOUVER ----------
Nir, I., Harrison, J.M., Haque, R., Low, M.J., Grandy, D.K., Rubinstein, M., et al. Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. J. Neurosci. 2002;22(6):2063-2073.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v22_n6_p2063_Nir [ ]