Nicotine and epibatidine triggered prolonged rise in calcium and TH gene transcription in PC12 cells.
The effect of epibatidine on regulation of [Ca2+]i and tyrosine hydroxylase (TH) transcription was examined. Epibatidine triggers a biphasic rise in [Ca2+]i in PC12 cells similar to that observed with nicotine. There was an immediate transient increase in [Ca2+]i and a subsequent sustained second elevation. In contrast to nicotine, the epibatidine-triggered increase in [Ca2+]i was independent of activation of alpha7 nicotinic acetylcholine receptors, as it was not altered by either methyllycaconitine or alpha-bungarotoxin. The second [Ca2+]i elevation involves calcium release from intracellular stores and is inhibited by dantrolene or xestospongin C. Epibatidine, like nicotine, elevated TH promoter driven reporter transcription, mostly mediated by the cyclic-AMP responsive motifs. Elevation in TH promoter activity requires Ca2+ and cAMP since it is inhibited by 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'-tetraacetic Acid Tetra (acetoxymethyl ester) (BAPTA-AM) or 2',5'-dideoxyadenosine (DDA). The results reveal that epibatidine can elevate [Ca2+]i in an alpha7 independent manner and nevertheless induce TH transcription.
Gueorguiev
Volodia D
VD
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
Frenz
Christopher M
CM
Ronald
Kimberly M
KM
Sabban
Esther L
EL
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C054634:methyllycaconitine; D016048:Dideoxyadenosine; D004533:Egtazic Acid; D009538:Nicotine; C021008:2',5'-dideoxyadenosine; D008156:Luciferases; D014446:Tyrosine 3-Monooxygenase; C082748:epibatidine; D002118:Calcium; D000157:Aconitine