{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T14:36:20Z","timestamp":1759588580006},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T00:00:00Z","timestamp":1149811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Melatonin and its autonomic regulation serve important physiological functions. We recently demonstrated that stimulation of beta\u2010adrenergic receptors only increases nighttime <jats:italic>arylalkylamine<\/jats:italic> N\u2010<jats:italic>acetyltransferase<\/jats:italic> (<jats:italic>Aa\u2010Nat<\/jats:italic>, the rate\u2010limiting enzyme in melatonin synthesis) mRNA levels in mouse pineal gland in vitro, which suggests that pineal clocks may gate <jats:italic>Aa\u2010Nat<\/jats:italic> gene expression. In the present study, our data reveal that cAMP analog increased <jats:italic>Aa\u2010Nat<\/jats:italic> at any time of day but only in the presence of ionomycin. Using Fura\u20102AM in ratiometric calcium measurements, we show that isoproterenol stimulation increased intracellular free calcium levels at night, contrary to previous reports. Further, intra\u2010 or extracellular calcium depletion suppressed the isoproterenol\u2010induced calcium responses as well as <jats:italic>Aa\u2010Nat<\/jats:italic> gene expression. These results suggest calcium may be a critical factor in isoproterenol\u2010induced <jats:italic>Aa\u2010Nat<\/jats:italic> gene expression, which may be limited in the daytime. We also found that basal intracellular calcium levels were lower during the night and responses to isoproterenol and KCl depolarization were more robust. In addition, pineals of <jats:italic>Cryptochrome<\/jats:italic> mutant mice exhibited no significant difference between day and nighttime basal calcium or isoproterenol response. Together, these results suggest that basal calcium levels in the pineal may be controlled by the endogenous pineal clock, which may influence calcium dynamics, cellular homeostasis and sensitivity to external stimulation. Although the mechanism underlying <jats:italic>Aa\u2010Nat<\/jats:italic> gene expression has been well studied, the role of calcium as a link between the pineal clock and <jats:italic>Aa\u2010Nat<\/jats:italic> gene expression has been underestimated in rodent pineals.<\/jats:p>","DOI":"10.1111\/j.1600-079x.2006.00341.x","type":"journal-article","created":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T10:26:51Z","timestamp":1149848811000},"page":"85-94","source":"Crossref","is-referenced-by-count":7,"title":["Role of calcium in the gating of isoproterenol\u2010induced <i>arylalkylamine<\/i> N\u2010<i>acetyltransferase<\/i> gene expression in the mouse pineal 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