Differential expression of immediate early genes in the superior cervical ganglion after nicotine treatment.
We examined the effects of single and multiple systemic injections of nicotine on the expression of five immediate early genes in the rat superior cervical ganglion by in situ hybridization histochemistry. A single nicotine injection resulted in a rapid and transient activation phase of nerve growth factor I-A, c-fos and jun-B at 20 min, and a later and less prominent activation of c-jun, which stayed high from 20 to 60 min. there was a parallel slow and long-lasting activation of jun-D, which remained high 4 h after nicotine treatment. Tyrosine hydroxylase mRNA, but not neuropeptide Y mRNA, was also induced by nicotine. Denervation of the ganglion did not prevent the induction of immediate early genes, but the nicotine antagonists hexamethonium and mecamylamine completely blocked the induction of immediate early genes, indicating that nicotine acted directly on receptors present on ganglion cells. When repeated nicotine injections were given, there was a refractory period of 1-2 h for c-fos, nerve growth factor I-A and jun-B induction. Repeated nicotine injections at 1-h intervals prevented about 80% of c-fos, nerve growth factor I-A and jun-B mRNA induction seen after a single injection. Because nicotine is known to induce immediate early genes in the adrenal glands as well, we examined whether similar kinetics of the gene induction could be seen in the adrenal medulla. However, no refractory period for repeated nicotine treatment or down regulation of the induction of the immediate early genes could be demonstrated in the adrenal medulla. The results show that sympathetic neurons respond to nicotine with altered expression of immediate early genes. Nicotine-induced expression of immediate early genes may be mediated and regulated by different factors in neuronal and endocrine noradrenergic cells.
Koistinaho
J
J
Department of Neurology, Department of Veterans Affairs Medical Center, San Francisco, CA 94121.
Pelto-Huikko
M
M
Sagar
S M
SM
Dagerlind
A
A
Roivainen
R
R
Hökfelt
T
T
D000818:Animals; D003714:Denervation; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics
D009414:Nerve Growth Factors; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D009538:Nicotine; D009116:Muscarine; D014446:Tyrosine 3-Monooxygenase