Regulation of Pineal α1B-Adrenergic Receptor mRNA: Day/Night Rhythm and β-Adrenergic Receptor/Cyclic AMP Control
- 1Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 (S.L.C., D.C.K.), 2Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3200 (S.K.M.), and 3Department of Physiology, Kings College London, University of London, London, England W8 7AH (D.S.)
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
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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
- Abbreviations:
- AR
- adrenergic receptor
- PKC
- protein kinase C
- NE
- norepinephrine
- SCN
- suprachiasmatic nuclei
- HEPES
- 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- G3PDH
- glyceraldehyde-3-phosphate dehydrogenase
- SSC
- standard saline citrate
- HEAT
- iodo-2-[β-(4-hydroxyphenyl)-ethylaminomethyl]tetralone
- VIP
- vasoactive intestinal peptide
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- Received October 31, 1996.
- Accepted December 17, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
