Abstract
Mammalian pineal function is regulated by norepinephrine acting through α1B- and β1-adrenergic receptors (ARs). Noradrenergic stimulation of α1B-ARs potentiates the β1-AR-driven increase in cAMP, serotoninN-acetyltransferase, and melatonin production. In the present study, we describe a 3-fold daily rhythm in mRNA-encoding α1B-ARs in the pineal gland, with a peak at midnight. Pharmacological studies indicate that this increase in α1B-AR mRNA is due to activation of β-ARs. Second messenger studies indicate that α1B-AR mRNA is increased by agents that increase cAMP, including dibutyryl cAMP, cholera toxin, forskolin, or vasoactive intestinal peptide. These observations indicate that α1B-AR mRNA can be physiologically regulated by a β-AR-dependent enhancement of cAMP. It also was observed that in vivo and in vitrochanges in α1B-AR mRNA are not accompanied by similar changes in α1B-AR binding, indicating that turnover of α1B-AR protein is significantly slower than that of α1B-AR mRNA and that post-transcriptional mechanisms play an important role in regulating α1B-AR binding.
Footnotes
- Received October 31, 1996.
- Accepted December 17, 1996.
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Send reprint requests to: Dr. David C. Klein, NIH, Bldg. 49, Room 5A38, Bethesda, MD 20892. E-mail:klein{at}helix.nih.gov
- The American Society for Pharmacology and Experimental Therapeutics
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