Abstract

Mammalian pineal function is regulated by norepinephrine acting through α_1B- and β₁-adrenergic receptors (ARs). Noradrenergic stimulation of α_1B-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 α_1B-ARs in the pineal gland, with a peak at midnight. Pharmacological studies indicate that this increase in α_1B-AR mRNA is due to activation of β-ARs. Second messenger studies indicate that α_1B-AR mRNA is increased by agents that increase cAMP, including dibutyryl cAMP, cholera toxin, forskolin, or vasoactive intestinal peptide. These observations indicate that α_1B-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 α_1B-AR mRNA are not accompanied by similar changes in α_1B-AR binding, indicating that turnover of α_1B-AR protein is significantly slower than that of α_1B-AR mRNA and that post-transcriptional mechanisms play an important role in regulating α_1B-AR binding.