期刊
JOURNAL OF PINEAL RESEARCH
卷 38, 期 3, 页码 170-175出版社
WILEY
DOI: 10.1111/j.1600-079X.2004.00189.x
关键词
cyclic 3 ',5 '-adenosine monophosphate; cyclic AMP responsive element-binding protein; dopamine receptors; melatonin; pinealocyte
资金
- NINDS NIH HHS [R01-NS40160-05] Funding Source: Medline
D-1- and D-2-dopamine receptors in the bovine pineal gland were previously identified and characterized. The data indicate that the density of D-1-dopamine receptors far exceeded that of D-2-dopamine receptors. In our previous study, the mRNA for both the D-1- and D-2-dopamine receptors which elucidated the status of dopamine and its possible involvement in the pineal function was identified. A selective D-1-agonist enhanced N-acetyltransferase (NAT) activity and increased the melatonin level, whereas, a selective D-2-agonist inhibited NAT activity and decreased the melatonin level. An attempt has been made in the present study to clarify the mechanism of dopamine in controlling melatonin production in bovine pineal. The level of intracellular cyclic 3',5'-adenosine monophosphate (cAMP) was determined after a 2-hr incubation of bovine pinealocytes with selected combinations of drugs. SKF 38393, a selective D-1-agonist, enhanced intracellular level of cAMP, and its effect was blocked by SCH 23390, a D-1-selective antagonist. In contrast quinpirole, a selective D-2-agonist, inhibited forskolin-stimulated intracellular level of cAMP while its effect was blocked by a D-2-selective antagonist, spiperone. In addition, the dopamine-dependent phosphorylation of the transcription factors, cAMP responsive element-binding protein (CREB) was investigated. Immunoblots showed that SKF 38393 enhanced CREB phosphorylation and the stimulatory effect was abolished by SCH 23390 whereas quinpirole inhibited forskolin-stimulated phosphorylated CREB production and the inhibitory effect was prevented by spiperone. Taken together with our previous data, the results indicate that activation of D-1-dopamine receptor in bovine pinealocyte stimulates NAT activity and enhances melatonin level whereas activation of D-2-dopamine receptor leads to an inhibitory effect and these stimulatory and inhibitory effects act, in part, via a cAMP-dependent transcription mechanism.
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