Neuronal regulation of c-fos, c-jun, and junB immediate-early genes in rat adrenal medulla

Abstract

We have applied in situ hybridization histochemistry, Northern analysis, and immunocytochemistry to study the regulation of the immediate-early gene (IEG) c-fos, c-jun, and junB mRNAs and the respective proteins in the rat adrenal medulla. Electrophoresis mobility shift assay was used to examine changes in AP-1 DNA binding activity. In nontreated rats the mRNA and protein levels for these three IEGs were low. Reflex stimulation of adrenal medulla elicited by a single capsaicin injection induced a rapid and marked elevation in the mRNA levels for these IEGs. Stimulation with nicotine also caused a drastic increase in the mRNA levels, whereas muscarine only induced moderate elevations. c-fos and c-jun were induced strongly in adrenaline cells and only weakly in noradrenaline cells. junB was upregulated mainly in adrenaline cells. The AP-1 DNA binding activity was low in control adrenals, whereas a marked increase was observed after nicotine treatment. Treatment of the animals with a nicotinic (chlorisondamine) or a muscarinic (atropine) receptor antagonist did not change the expression of IEGs studied. The combination of the two drugs, however elevated the mRNA levels for all three IEGs, especially for junB. Pretreatment of the rats with chlorisondamine alone or in combination with atropine diminished the capsaicin-induced increase in c-fos, whereas atropine alone was less efficient. Increase in c-jun mRNA was not affected by these drugs. The capsaicin-induced elevation of junB mRNA levels was not influenced by chlorisondamine or atropine alone, whereas both combined potentiated the effect of capsaicin. The present results demonstrate that neurotransmitters released from splanchnic nerve terminals induce expression of c-fos, c-jun, and junB in adrenal chromaffin cells which results in increased AP-1 DNA binding activity. Although stimulation of both nicotinic and muscarinic cholinergic receptors may mediate the induction of these IEGs, it is possible that also another neurotransmitter(s), in addition to ACh, released from splanchnic nerve terminals is involved in the regulation of their expression, especially of c-jun and junB.

Different Expression of Immediate-Early Genes in the Rat Paraventricular Nucleus Induced by Stress: Relation to Corticotropin-Releasing Factor Gene Transcription.

“…Recent studies have demonstrated that glutamate is a major mediator of fast excitatory transmission in the region of the PVN where CRF cell bodies are located [25]. The temporal pattern of expression of fos and jun family members apparent in the present study in response to stress is similar to that observed in the adrenal medulla in response to capsaicin [23]. In the latter study, the induction of c f os was most rapid, with the abundance of c f os mRNA reaching a peak at 30 min.…”

“…The abundance of c jun and jun-B mRNAs was maximal at 1 h. The extent of induction of these IEGs was also similar in the two studies. The capsaicin-induced increases in the abundance of cfos and jun-B mRNAs were reduced by treatment of the cells with chlonsondamine and atropine, suggesting that stimulation of both nicotinic and muscarinic receptors may mediate the induction of these IEGs [23]. Glutamate has also been shown to increase the abundance of c f os, c jun, and jun-B mRNAs in primary cultures of neurons from cerebral cortex and striatum [26].…”

“…Neurons respond to a variety of extracellular stimuli, including growth factors, hormones, and potassium or neurotransmitter-induced depolarization, by manifesting rapid and transient differential induction of IEGs [4,22,23]. Depending on the expression pattern of IEGs, one may speculate which candidate neurotransmitter activates PVN neurons.…”

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

“…Regulation of neurotransmitter release The activation of nAChRs can influence gene expression for immediate early genes and genes involved in transmitter synthesis [15,52,59,60] . In the chick ciliary ganglion [61] , the nAChR-mediated control of transcription relies on calcium influx and calcium release from internal stores to activate first CaMKII/IV, and then ERK/MAPK.…”

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

“…Nicotinic transmission can also influence gene expression as originally shown for immediate early genes and genes involved in transmitter synthesis (Chalazonitis and Zigmond, 1980;Greenberg et al, 1986;Pelto-Huikko et al, 1995;Salminen et al, 1999;Gueorguiev et al, 2000). The underlying mechanisms have been examined in some detail in the chick ciliary ganglion .…”