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Involvement of α7 Nicotinic Acetylcholine Receptors in Activation of Tyrosine Hydroxylase and Dopamine β‐Hydroxylase Gene Expression in PC12 Cells
Author(s) -
Gueorguiev Volodia D.,
Zeman Richard J.,
Meyer Edwin M.,
Sabban Esther L.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751997.x
Subject(s) - methyllycaconitine , tyrosine hydroxylase , nicotine , endocrinology , medicine , chemistry , nicotinic agonist , acetylcholine receptor , dopamine , acetylcholine , receptor , catecholamine , stimulation , nicotinic acetylcholine receptor , biology
Nicotine treatment increases intracellular free Ca 2+ concentration [Ca 2+ ] i , stimulates catecholamine release, and elevates gene expression for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and dopamine β‐hydroxylase (DBH). However, the type of nicotinic acetylcholine receptors (nAChRs) mediating these events is unclear. The nAChR receptor antagonists α‐bungarotoxin (αBTX) and methyllycaconitine greatly reduced the nicotine‐triggered initial transient rise in [Ca 2+ ] i and prevented the second prolonged elevation of [Ca 2+ ] i , suggesting the involvement of α7 nAChRs. Two specific α7 nicotinic agonists, 3‐(2,4‐dimethoxybenzilidene)anabaseine (DMXB) and E,E ‐3‐(cinnamylidene)anabaseine (3‐CA), were found to elicit a small, delayed increase in [Ca 2+ ] i with kinetics and magnitude similar to the second elevation observed with nicotine. This increase was inhibited by the inositol trisphosphate receptor antagonist xestospongin C. Exposure to 3‐CA or DMXB for 6 or 24 h elevated TH and DBH mRNA levels two‐ to fourfold over control levels. These agonists were more effective than nicotine alone in increasing TH and DBH gene expression and significantly elevated [Ca 2+ ] i for up to 6 h. The increase in [Ca 2+ ] i or the elevation in TH mRNA by 3‐CA was completely inhibited by αBTX. This study, for the first time, implicates stimulation of α7 nAChRs in the activation of TH and DBH gene expression.