title: High-dose glucocorticoids induce decreases calcium in hypothalamus neurons via plasma membrane Ca(2+) pumps.
abstract: In our previous studies, we occasionally found that high-dose glucocorticoids (GC) induced decrease in [Ca(2+)](i) in hypothalamus neurons. In previous articles, modulation of Ca(2+) channels by GC has been shown to contribute to the elementary regulation of several neuronal functions. However, little is known about the regulation of the Ca efflux pathways that counterbalance the Ca(2+) influx in neurons caused by high-dose GC. In this study, we demonstrate that a high-dose of GC (10 M dexamethasone) caused a 20% decrease in [Ca(2+)](i) within 2 s in cultured hypothalamic neurons; furthermore, we show that an antagonist of the GC receptor blocks this action. To ascertain the temporal sequence of relevant calcium transport mechanisms we selectively blocked the main calcium transporters, including sodium/calcium exchanger (NCX), plasma membrane calcium pumps (PMCA), and P-type Ca(2+)-ATPases of the sarcoplasmic reticulum (SERCA). The GC-induced [Ca(2+)](i) decrease disappeared completely when PMCA was blocked, but not when NCX and SERCA were blocked. These results suggest that high-dose GC (10(-6) M) rapidly decreases [Ca(2+)](i) by activating PMCA but not NCX or SERCA.
authors.affiliation: Department of Clinical Biochemistry, Laboratory Sciences, Burns and Combined Injury, Institute for Traffic Medicine, Research Institute of Surgery & Daping Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Chen
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Xiu-Zhu
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Wu-Chao
authors.initials: WC
authors.lastname: Wang
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Liu
authors.forename: Zai-Yun
authors.initials: ZY
authors.lastname: Long
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Xu
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D019831:Sodium-Calcium Exchanger; D003907:Dexamethasone; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium