Adenosine A1 receptors regulate the response of the mouse circadian clock to light.
The purine nucleoside, adenosine, has been implicated in the regulation of circadian phase in the hamster. In the current report, we present pharmacological evidence supporting the involvement of adenosine A1 receptors in the regulation of the response of the circadian clock to light in mice. Systemic injection of the selective adenosine A1 receptor agonist, N(6)-cyclohexyladenosine (CHA; 0.3 mg/kg) resulted in a 49% reduction (P<0.05) in the magnitude of light-induced phase delays. The inhibitory effect of CHA on light-induced phase delays was dose dependent over a range of 0.1 to 5 mg/kg with an apparent EC(50) of 0.3 mg/kg. Prior administration of the selective adenosine A1 receptor antagonist dipropylcyclopentylxanthine (DPCPX; 1 mg/kg) completely blocked the effect of CHA on photic phase delays. Finally, CHA significantly attenuated light-induced phospho-extracellular signal-related kinases (ERK) immunoreactivity in the mouse suprachiasmatic nucleus (SCN), consistent with a mode of action involving events that occur early in the signaling cascade through which photic information is conveyed to the circadian clock. These data indicate that the role of adenosine in the regulation of circadian phase is similar in mice and hamsters.
Sigworth
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Department of Biology and Biochemistry, University of Houston, 4800 Calhoun Street, Houston, TX 77204-5513, USA.
Rea
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000201:enzymology / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019950:Mitogen-Activated Protein Kinase 1; D000241:Adenosine