Diurnal variation of the adenylyl cyclase type 1 in the rat pineal gland.
Nocturnal melatonin production in the pineal gland is under the control of norepinephrine released from superior cervical ganglia afferents in a rhythmic manner, and of cyclic AMP. Cyclic AMP increases the expression of serotonin N-acetyltransferase and of inducible cAMP early repressor that undergo circadian oscillations crucial for the maintenance and regulation of the biological clock. In the present study, we demonstrate a circadian pattern of expression of the calcium/calmodulin activated adenylyl cyclase type 1 (AC1) mRNA in the rat pineal gland. In situ hybridization revealed that maximal AC1 mRNA expression occurred 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 noradrenergic innervation of the pineal gland and by the environmental light conditions. Finally, we observed a circadian responsiveness of the pineal AC activity to calcium/calmodulin, with a lag due to the processing of the protein. At midday, AC activity was inhibited by calcium (40%) either in the presence or absence of calmodulin, while at night the enzyme was markedly (3-fold) activated by the calcium-calmodulin complex. 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.
Tzavara
E T
ET
Institut National de la Santé et de la Recherche Médicale, Hopital Henri Mondor, Creteil, France.
Pouille
Y
Y
Defer
N
N
Hanoune
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002940:Circadian Rhythm; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D017403:In Situ Hybridization; D008027:Light; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000502:physiology; D010870:Pineal Gland / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D002147:Calmodulin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; D002118:Calcium; D009638:Norepinephrine