Differing temporal roles of Ca²⁺ and cAMP in nicotine-elicited elevation of tyrosine hydroxylase mRNA

Abstract

The involvement of cAMP- and Ca2+-mediated pathways in the activation of tyrosine hydroxylase (TH) gene expression by nicotine was examined in PC-12 cells. Extracellular Ca2+ and elevations in intracellular Ca2+ concentration ([Ca2+]i) were required for nicotine to increase TH mRNA. The nicotine-elicited rapid rise in [Ca2+]iwas inhibited by blockers of either L-type or N-type, and to a lesser extent P/Q-, but not T-type, voltage-gated Ca2+ channels. With continual nicotine treatment, [Ca2+]ireturned to basal levels within 3–4 min. After a lag of ∼5–10 min, there was a smaller elevation in [Ca2+]ithat persisted for 6 h and displayed different responsiveness to Ca2+ channel blockers. This second phase of elevated [Ca2+]iwas blocked by an inhibitor of store-operated Ca2+ channels, consistent with the observed generation of inositol trisphosphate. 1,2-Bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM (BAPTA-AM), when added before or 2 h after nicotine, prevented elevation of TH mRNA. Nicotine treatment significantly raised cAMP levels. Addition of the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine (DDA) prevented the nicotine-elicited phosphorylation of cAMP response element binding protein. DDA also blocked the elevation of TH mRNA only when added after the initial transient rise in [Ca2+]iand not after 1 h. This study reveals that several temporal phases are involved in the induction of TH gene expression by nicotine, each of them with differing requirements for Ca2+ and cAMP.

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

“…Long-term treatment with nicotine increases the concentration of TH-mRNA and, consequently, TH-activity, both in vivo and in chromaffin cells [62] . This effect is calcium-dependent and mediated by protein kinase A (PKA) [63] . The nicotine-induced activation of expression of the gene encoding TH requires a prolonged increase in calcium concentration, and the activation of store-dependent calcium channels [63] and ERK/MAPK [64] .…”

Region-specific transcriptional response to chronic nicotine in rat brain

“…We identified the signaling pathways, such as mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGRF), phosphatidylinositol, to which these genes belong. The relevance of these pathways to nicotine administration was also assessed based on the available literature [52,16,32].…”

“…Nicotine also has been shown to elevate intracellular calcium levels upon activation of the store-operated calcium channels possibly by an increase in the D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) production [16].In this study we identified a number of genes, such as profilin 1, Ins(1,4,5)P 3 3-kinase B, and PTEN, involved in Ins(1,4,5)P 3 turnover as well as intracellular calcium homeostasis, as potential modulators/targets of nicotine in rat brain. Profilin negatively regulates the phophoinositide signaling pathway by binding with phosphatidylinositol 4,5-bisphosphate (PIP2) and preventing the formation of Ins(1,4,5)P and diacylglycerol via inhibition of the phospholipase C gamma 1 hydrolysis [14].…”

Human colon adenocarcinoma HT-29 cell: Electrochemistry and nicotine stimulation

“…Colorectal cancer patients suffer from various forms of psychological stress reflected in elevated plasma catecholamines levels [7], and it has been shown that HT-29 human colon carcinoma cells, as well as other cancer cells, express α7-nicotinic acetylcholine receptor (α7-nAChR), catecholamine-synthesizing enzymes (tyrosine hydroxylase (TH), and DOPA decarboxylase (DDC), dopamine-β-hydroxylase (DβH), phenylethanolamine N-methyltransferase (PNMT) and adrenergic receptors [8,9,10].…”

“…Through the activated ionic channels or due to the membrane depolarization, Ca 2+ can enter the cells and favour activation (i.e., phosphorylation) of the transcription factor CREB (cAMP response element-binding protein), which in turn modifies gene expression [10,12,13]. Scheme 1.…”