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| Research article summary (published 20 Jan 2009): |
Essential roles of dopamine D4 receptors and the type 1 adenylyl cyclase in photic control of cyclic AMP in photoreceptor cells.
Full Abstract
Light and dopamine regulate many physiological functions in the vertebrate retina. Light exposure decreases cyclic AMP formation in photoreceptor cells. Dopamine D(4) receptor (D(4)R) activation promotes light adaptation and suppresses the light-sensitive pool of cyclic AMP in photoreceptor cells. The key signaling pathways involved in regulating cyclic AMP in photoreceptor cells have not been identified. In the present study, we show that the light- and D(4)R-signaling pathways converge on the type 1 Ca(2+)/calmodulin-stimulated adenylyl cyclase (AC1) to regulate cyclic AMP synthesis in photoreceptor cells. In addition, we present evidence that D(4)R activation tonically regulates the expression of AC1 in photoreceptors. In retinas of mice with targeted deletion of the gene (Adcy1) encoding AC1, cyclic AMP levels and Ca(2+)/calmodulin-stimulated adenylyl cyclase activity are markedly reduced, and cyclic AMP accumulation is unaffected by either light or D(4)R activation. Similarly, in mice with disruption of the gene (Drd4) encoding D(4)R, cyclic AMP levels in the dark-adapted retina are significantly lower compared to wild-type retina and are unresponsive to light. These changes in Drd4-/- mice were accompanied by significantly lower Adcy1 mRNA levels in photoreceptor cells and lower Ca(2+)/calmodulin-stimulated adenylyl cyclase activity in retinal membranes compared with wild-type controls. Reduced levels of Adcy1 mRNA were also observed in retinas of wild-type mice treated chronically with a D(4)R antagonist, L-745870. Thus, activation of D(4)R is required for normal expression of AC1 and for the regulation of its catalytic activity by light. These observations illustrate a novel mechanism for cross-talk between dopamine and photic signaling pathways regulating cyclic AMP in photoreceptor cells.
Author information
Author/s: Jackson, Chad R (CR); Chaurasia, Shyam S (SS); Zhou, Hong (H); Haque, Rashidul (R); Storm, Daniel R (DR); Iuvone, P Michael (PM);
Affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Grants: P30EY006360 (Agency:NEI NIH HHS) ; R01EY004864 (Agency:NEI NIH HHS) ; R01EY014764 (Agency:NEI NIH HHS) ; T32EY007092 (Agency:NEI NIH HHS)
Journal and publication information
Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)
Reference: 2009-Apr; vol 109 (issue 1) : pp 148-57
Dates: Created 2009/03/18; Completed 2009/04/13; Revised 2009/09/03;
PMID: 19166506, status: MEDLINE (last retrieved date: 9/4/2009)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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Associated Chemicals: Dopamine Antagonists (0) ; Receptors, Dopamine D4 (137750-34-6) ; Cyclic AMP (60-92-4) ; Adenylate Cyclase (EC 4.6.1.1) ; adenylyl cyclase 1 (EC 4.6.1.1)Related articles
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