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. Epibatidme triggers a biphasic rise in [Ca2+](i) in PC12 cells similar to that observed with nicotine. There was an immediatt, 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. (C) 2004 Elsevier B.V. All rights reserved.