{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:20:42Z","timestamp":1762100442265,"version":"3.32.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p>Norepinephrine (NE) is one of the major neurotransmitters that determine melatonin production in the pineal gland. Although a substantial amount of Ca<jats:sup>2+<\/jats:sup>influx is triggered by NE, the Ca<jats:sup>2+<\/jats:sup>entry pathway and its physiological relevance have not been elucidated adequately. Herein we report that the Ca<jats:sup>2+<\/jats:sup>influx triggered by NE significantly regulates the protein level of serotonin N-acetyltransferase, or arylalkylamine N-acetyltransferase (AANAT), a critical enzyme in melatonin production, and is responsible for maintaining the Ca<jats:sup>2+<\/jats:sup>response after repetitive stimulation. Ca<jats:sup>2+<\/jats:sup>entry evoked by NE was dependent on PLC activation. NE evoked a substantial amount of Ca<jats:sup>2+<\/jats:sup>entry even after cells were treated with 1-oleoyl-2-acetyl- sn-glycerol (OAG), an analog of diacylglycerol. To the contrary, further OAG treatment after cells had been exposed to OAG did not evoke additional Ca<jats:sup>2+<\/jats:sup>entry. Moreover, NE failed to induce further Ca<jats:sup>2+<\/jats:sup>entry after the development of Ca<jats:sup>2+<\/jats:sup>entry induced by thapsigargin (Tg), suggesting that the pathway of Ca<jats:sup>2+<\/jats:sup>entry induced by NE might be identical to that of Tg. Interestingly, Ca<jats:sup>2+<\/jats:sup>entry evoked by NE or Tg induced membrane hyperpolarization that was reversed by iberiotoxin (IBTX), a specific inhibitor of large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK) channels. Moreover, IBTX-sensitive BK current was observed during application of NE, suggesting that activation of the BK channels was responsible for the hyperpolarization. Furthermore, the activation of BK channels triggered by NE contributed to regulation of the protein level of AANAT. Collectively, these results suggest that NE triggers Ca<jats:sup>2+<\/jats:sup>entry coupled to BK channels and that NE-induced Ca<jats:sup>2+<\/jats:sup>entry is important in the regulation of AANAT.<\/jats:p>","DOI":"10.1152\/ajpcell.00343.2005","type":"journal-article","created":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T01:24:21Z","timestamp":1131585861000},"page":"C1060-C1066","source":"Crossref","is-referenced-by-count":19,"title":["Norepinephrine activates store-operated Ca<sup>2+<\/sup>entry coupled to large-conductance Ca<sup>2+<\/sup>-activated K<sup>+<\/sup>channels in rat pinealocytes"],"prefix":"10.1152","volume":"290","author":[{"given":"So-Young","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Hwa","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Mi","family":"Hur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin Ok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyong-Tai","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Aguayo LGand Weight FF.Characterization of membrane currents in dissociated adult rat pineal cells.J Physiol405: 397\u2013419, 1988.","DOI":"10.1113\/jphysiol.1988.sp017339"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Berridge MJ, Bootman MD, and Lipp P.Calcium: a life and death signal.Nature395: 645\u2013648, 1998.","DOI":"10.1038\/27094"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Cena V, Halperin JI, Yeandle S, and Klein DC.Norepinephrine stimulates potassium efflux from pinealocytes: evidence for involvement of biochemical \u201cAND\u201d gate operated by calcium and adenosine 3\u2032,5\u2032-monophosphate.Endocrinology128: 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