Dopamine D₄ receptor activation controls circadian timing of the adenylyl cyclase 1/cyclic AMP signaling system in mouse retina. Eur J Neurosci 2011 Jul;34(1):57-64
Date
06/17/2011Pubmed ID
21676039Pubmed Central ID
PMC3129439DOI
10.1111/j.1460-9568.2011.07734.xScopus ID
2-s2.0-79959994092 (requires institutional sign-in at Scopus site) 63 CitationsAbstract
In the mammalian retina, dopamine binding to the dopamine D₄ receptor (D₄R) affects a light-sensitive pool of cyclic AMP by negatively coupling to the type 1 adenylyl cyclase (AC1). AC1 is the primary enzyme controlling cyclic AMP production in dark-adapted photoreceptors. A previous study demonstrated that expression of the gene encoding AC1, Adcy1, is downregulated in mice lacking Drd4, the gene encoding the D₄R. The present investigation provides evidence that D₄R activation entrains the circadian rhythm of Adcy1 mRNA expression. Diurnal and circadian rhythms of Drd4 and Adcy1 mRNA levels were observed in wild-type mouse retina. Also, rhythms in the Ca²⁺-stimulated AC activity and cyclic AMP levels were observed. However, these rhythmic activities were damped or undetectable in mice lacking the D₄R. Pharmacologically activating the D₄R 4 h before its normal stimulation at light onset in the morning advances the phase of the Adcy1 mRNA expression pattern. These data demonstrate that stimulating the D₄R is essential in maintaining the normal rhythmic production of AC1 from transcript to enzyme activity. Thus, dopamine/D₄R signaling is a novel zeitgeber that entrains the rhythm of Adcy1 expression and, consequently, modulates the rhythmic synthesis of cyclic AMP in mouse retina.
Author List
Jackson CR, Chaurasia SS, Hwang CK, Iuvone PMAuthor
Shyam S. Chaurasia PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenylyl CyclasesAnimals
Circadian Rhythm
Cyclic AMP
Dark Adaptation
Dopamine
Light
Mice
Mice, Inbred C57BL
Mice, Knockout
Photic Stimulation
Photoreceptor Cells
Receptors, Dopamine D4
Retina
Signal Transduction
