title: Upregulation of norepinephrine transporter function by prolonged exposure to nicotine in cultured bovine adrenal medullary cells.
abstract: Nicotine acts on nicotinic acetylcholine receptors in the adrenal medulla and brain, thereby stimulating the release of monoamines such as norepinephrine (NE). In the present study, we examined the effects of prolonged exposure to nicotine on NE transporter (NET) activity in cultured bovine adrenal medullary cells. Treatment of adrenal medullary cells with nicotine increased [(3)H]NE uptake in both a time- (1-5 days) and concentration-dependent (0.1-10 muM) manner. Kinetic analysis showed that nicotine induced an increase in the V (max) of [(3)H]NE uptake with little change in K (m). This increase in NET activity was blocked by cycloheximide, an inhibitor of ribosomal protein synthesis, but not by actinomycin D, a DNA-dependent RNA polymerase inhibitor. [(3)H]NE uptake induced by nicotine was strongly inhibited by hexamethonium and mecamylamine but not by alpha-bungarotoxin, and was abolished by elimination of Ca(2+) from the culture medium. KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II, attenuated not only nicotine-induced [(3)H]NE uptake but also (45)Ca(2+) influx in the cells. The present findings suggest that long-term exposure to nicotine increases NET activity through a Ca(2+)-dependent post-transcriptional process in the adrenal medulla.
authors.affiliation: Department of Rehabilitation Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.forename: Satoru
authors.initials: S
authors.lastname: Saeki
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Yumi
authors.initials: Y
authors.lastname: Furuno
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Kenji
authors.initials: K
authors.lastname: Hachisuka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018722:Nicotinic Agonists; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D009538:Nicotine; D002118:Calcium; D009638:Norepinephrine