title: Norepinephrine activates store-operated Ca2+ entry coupled to large-conductance Ca2+-activated K+ channels in rat pinealocytes.
abstract: Norepinephrine (NE) is one of the major neurotransmitters that determine melatonin production in the pineal gland. Although a substantial amount of Ca(2+) influx is triggered by NE, the Ca(2+) entry pathway and its physiological relevance have not been elucidated adequately. Herein we report that the Ca(2+) 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(2+) response after repetitive stimulation. Ca(2+) entry evoked by NE was dependent on PLC activation. NE evoked a substantial amount of Ca(2+) 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(2+) entry. Moreover, NE failed to induce further Ca(2+) entry after the development of Ca(2+) entry induced by thapsigargin (Tg), suggesting that the pathway of Ca(2+) entry induced by NE might be identical to that of Tg. Interestingly, Ca(2+) entry evoked by NE or Tg induced membrane hyperpolarization that was reversed by iberiotoxin (IBTX), a specific inhibitor of large-conductance Ca(2+)-activated K(+) (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(2+) entry coupled to BK channels and that NE-induced Ca(2+) entry is important in the regulation of AANAT.
authors.affiliation: Division of Molecular and Life Science, National Core Research Center for System Bio-Dynamics, Department of Life Science, Pohang University of Science and Technology, Pohang, Kyung-buk 790-784, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Bo-Hwa
authors.initials: BH
authors.lastname: Choi
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Hur
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chin Ok
authors.initials: CO
authors.lastname: Lee
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism; D010870:Pineal Gland / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D019284:Thapsigargin; C064719:iberiotoxin; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine