DIURNAL-VARIATION OF THE ADENYLYL-CYCLASE TYPE-1 IN THE RAT PINEAL-GLAND

Nocturnal melatonin production in the pineal gland is under the contro l of norepinephrine released from superior cervical ganglia afferents in a rhythmic manner, and of cyclic AMP, Cyclic AMP increases the expr ession of serotonin N-acetyltransferase and of inducible cAMP early re pressor that undergo circadian oscillations crucial for the maintenanc e and regulation of the biological clock. In the present study, we dem onstrate a circadian pattern of expression of the calcium/calmodulin a ctivated adenylyl cyclase type 1 (AC1) mRNA in the rat pineal gland, I n situ hybridization revealed that maximal AC1 mRNA expression occurre d at midday (12:00-15:00), with a very low signal at night (0:00-3:00) . We established that this rhythmic pattern was controlled by the nora drenergic innervation of the pineal gland and by the environmental lig ht conditions, Finally, we observed a circadian responsiveness of the pineal AC activity to calcium/calmodulin, with a lag due to the proces sing of the protein. At midday, AC activity was inhibited by calcium ( 40%) either in the presence or absence of calmodulin, while at night t he enzyme was markedly (3-fold) activated by the calcium-calmodulin co mplex. These findings suggest (i) the involvement of AC1 acting as the center of a gating mechanism, between cyclic AMP and calcium signals, important for the fine tuning of the pineal circadian rhythm; and (ii ) a possible regulation of cyclic AMP on the expression of AC1 in the rat pineal gland.