Effects of short- and long-term nicotine treatment on intracellular calcium and tyrosine hydroxylase gene expression.
It is important to determine how the signaling pathways for the short-term effects of nicotine (catecholamine secretion, phosphorylation of tyrosine hydroxylase) differ from those required for changes in gene expression. Our aim was to distinguish the pathways involved in short- and long-term nicotinic stimulation. PC12 cells were treated with several concentrations of nicotine from 10 micro M to 1 mM. All elicited a rapid and transient rise in [Ca(2+)](i), which was concentration dependent. After several minutes of continued exposure, a second smaller sustained rise in [Ca(2+)](i) was only observed with intermediate concentrations of nicotine (50-200 micro M). This sustained rise was not observed in cells pretreated with alpha-bungarotoxin (alpha-BTX). alpha-BTX also prevented the elevation of tyrosine hydroxylase mRNA by nicotine. The effects of brief and prolonged treatment with nicotine on the signaling pathways involved in changes in [Ca(2+)](i) and induction of tyrosine hydroxylase gene expression are summarized. The results indicate that nicotine may elicit different signaling pathways depending on the concentration. The sustained elevation of [Ca(2+)](i) via activation of alpha7 nAChRs is proposed as the mechanism leading to increased tyrosine hydroxylase gene expression.
Sabban
Esther L
EL
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA. sabban@nymc.edu
Gueorguiev
Volodia D
VD
D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005786:Gene Expression Regulation; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics*
D002038:Bungarotoxins; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D002118:Calcium