title: Dopamine D₄ receptor activation controls circadian timing of the adenylyl cyclase 1/cyclic AMP signaling system in mouse retina.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Jackson
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chaurasia
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Hwang
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D003623:Dark Adaptation / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000166:cytology / Q000502:physiology; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D050638:Receptors, Dopamine D4; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; D004298:Dopamine