Regulation of pineal alpha1B-adrenergic receptor mRNA: day/night rhythm and beta-adrenergic receptor/cyclic AMP control.

Mammalian pineal function is regulated by norepinephrine acting through alpha1beta- and beta1-adrenergic receptors (ARs). Noradrenergic stimulation of alpha1beta-ARs potentiates the beta1-AR-driven increase in cAMP, serotonin N-acetyltransferase, and melatonin production. In the present study, we describe a 3-fold daily rhythm in mRNA-encoding alpha1beta-ARs in the pineal gland, with a peak at midnight. Pharmacological studies indicate that this increase in alpha1beta-AR mRNA is due to activation of beta-ARs. Second messenger studies indicate that alpha1beta-AR mRNA is increased by agents that increase cAMP, including dibutyryl cAMP, cholera toxin, forskolin, or vasoactive intestinal peptide. These observations indicate that alpha1beta-AR mRNA can be physiologically regulated by a beta-AR-dependent enhancement of cAMP. It also was observed that in vivo and in vitro changes in alpha1beta-AR mRNA are not accompanied by similar changes in alpha1beta-AR binding, indicating that turnover of alpha1beta-AR protein is significantly slower than that of alpha1beta-AR mRNA and that post-transcriptional mechanisms play an important role in regulating alpha1beta-AR binding.