Faculty Collaboration Database

Resetting the circadian clock in cultured Xenopus eyecups: regulation of retinal melatonin rhythms by light and D2 dopamine receptors. J Neurosci 1991 Oct;11(10):2959-71

Date

10/01/1991

Pubmed ID

1682423

Pubmed Central ID

PMC6575428

DOI

10.1523/JNEUROSCI.11-10-02959.1991

Scopus ID

2-s2.0-0025943811 (requires institutional sign-in at Scopus site)   172 Citations

Abstract

A circadian oscillator is located within the eye of Xenopus laevis. This oscillator regulates retinal melatonin synthesis, stimulating it at night. The primary goal of the studies reported here was to define input pathways to this circadian oscillator as a step toward identification of circadian clock mechanisms. A flow-through superfusion culture system was developed to monitor circadian rhythms of melatonin release from individual eyecups. This system was used to determine the effects of light and dopaminergic agents on melatonin production and on the phase of the circadian oscillator. Six hour light pulses suppressed melatonin production and reset the phase of the free-running melatonin rhythm. Light pulses caused phase delays when applied during the early subjective night, phase advances when applied during the late subjective night, and no phase shift when applied during the subjective day. Dopamine receptor agonists mimicked light in suppressing melatonin release and resetting the phase of the circadian rhythm. The phase-response relationship for phase shifts induced by quinpirole, a D2 dopamine receptor agonist, was similar to that for phase shifts induced by light. Pharmacological analysis with selective catecholamine receptor agonists and antagonists indicated that there are pathways to the melatonin-generating system and the circadian oscillator that include D2 dopamine receptors. A D2 receptor antagonist, eticlopride, completely blocked the effects of dopamine on melatonin release and on circadian phase. However, eticlopride did not alter similar effects induced by light, indicating that dopamine-independent pathways exist for light input to these systems. The effects of light and quinpirole on melatonin release and circadian phase were not additive, indicating that the pathways converge. These pathways to the circadian oscillator in the retina present new avenues for pursuit of cellular circadian clock mechanisms.

Author List

Cahill GM, Besharse JC

MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Circadian Rhythm
Dopamine Agents
Ergolines
Light
Male
Melatonin
Ocular Physiological Phenomena
Organ Culture Techniques
Quinpirole
Receptors, Dopamine
Receptors, Dopamine D2
Retina
Xenopus laevis