REGULATION OF PINEAL ALPHA(1B)-ADRENERGIC RECEPTOR MESSENGER-RNA - DAY NIGHT RHYTHM AND BETA-ADRENERGIC-RECEPTOR CYCLIC-AMP CONTROL/

Mammalian pineal function is regulated by norepinephrine acting throug h alpha(1B)- and beta(1)-adrenergic receptors (ARs). Noradrenergic sti mulation of alpha(1B)-ARs potentiates the beta(1)-AR-driven increase i n cAMP, serotonin N-acetyltransferase, and melatonin production. In th e present study, we describe a 3-fold daily rhythm in mRNA-encoding al pha(1B)-ARs in the pineal gland, with a peak at midnight. Pharmacologi cal studies indicate that this increase in alpha(1B)-AR mRNA is due to activation of beta-ARs. Second messenger studies indicate that alpha( 1B)-AR mRNA is increased by agents that increase cAMP, including dibut yryl cAMP, cholera toxin, forskolin, or vasoactive intestinal peptide. These observations indicate that alpha(1B)-AR mRNA can be physiologic ally regulated by a beta-AR-dependent enhancement of cAMP. It also was observed that in vivo and in vitro changes in alpha(1B)-AR mRNA are n ot accompanied by similar changes in alpha(1B)-AR binding, indicating that turnover of alpha(1B)-AR protein is significantly slower than tha t of alpha(1B)-AR mRNA and that post-transcriptional mechanisms play a n important role in regulating alpha(1B)-AR binding.