Nicotine and epibatidine triggered prolonged rise in calcium and TH gene transcription in PC12 cells

Abstract The effect of epibatidine on regulation of [Ca 2+ ] i and tyrosine hydroxylase (TH) transcription was examined. Epibatidine triggers a biphasic rise in [Ca 2+ ] i in PC12 cells similar to that observed with nicotine. There was an immediate transient increase in [Ca 2+ ] i and a subsequent sustained second elevation. In contrast to nicotine, the epibatidine-triggered increase in [Ca 2+ ] i was independent of activation of α7 nicotinic acetylcholine receptors, as it was not altered by either methyllycaconitine or α-bungarotoxin. The second [Ca 2+ ] 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 Ca 2+ 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 [Ca 2+ ] i in an α7 independent manner and nevertheless induce TH transcription.