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.