title: Nongenomic inhibition of catecholamine secretion by 17beta-estradiol in PC12 cells.
abstract: We investigated the effects of 17beta-estradiol, an estrogen, on [(3)H]norepinephrine ([(3)H]NE) secretion in PC12 cells. Pretreatment with 17beta-estradiol reduced 70 mM K(+)-induced [(3)H]NE secretion in a concentration-dependent manner with a half-maximal inhibitory concentration (IC(50)) of 2 +/- 1 microM. The 70 mM K(+)-induced cytosolic free Ca(2+) concentration ([Ca(2+)](i)) rise was also reduced when the cells were treated with 17beta-estradiol (IC(50) = 15 +/- 2 microM). Studies with voltage-sensitive calcium channel (VSCC) antagonists such as nifedipine and omega-conotoxin GVIA revealed that both L- and N-type VSCCs were affected by 17beta-estradiol treatment. The 17beta-estradiol effect was not changed by pretreatment of the cells with actinomycin D and cycloheximide for 5 h. In addition, treatment with pertussis or cholera toxin did not affect the inhibitory effect of 17beta-estradiol. 17beta-Estradiol also inhibited the ATP-induced [(3)H]NE secretion and [Ca(2+)](i) rise. In PC12 cells, the ATP-induced [Ca(2+)](i) rise is known to occur through P2X(2) receptors, the P2Y(2)-mediated phospholipase C (PLC) pathway, and VSCCs. 17beta-Estradiol pretreatment during complete inhibition of the PLC pathway and VSCCs inhibited the ATP-induced [Ca(2+)](i) rise. Our results suggest that 17beta-estradiol inhibits catecholamine secretion by inhibiting L- and N-type Ca(2+) channels and P2X(2) receptors in a nongenomic manner.
authors.affiliation: Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.forename: E M
authors.initials: EM
authors.lastname: Hur
authors.forename: T J
authors.initials: TJ
authors.lastname: Park
authors.forename: K T
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000493:pharmacokinetics*; D016716:PC12 Cells; D010627:Phenethylamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058476:Receptors, Purinergic P2X2; D013566:Sympathomimetics / Q000493:pharmacokinetics*; D014316:Tritium
chemical_list: D000959:Antihypertensive Agents; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D007476:Ionophores; D010627:Phenethylamines; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D013566:Sympathomimetics; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D004958:Estradiol; D015759:Ionomycin; D000241:Adenosine; D011188:Potassium; D001920:Bradykinin; D002118:Calcium; D009638:Norepinephrine