Inhibition of L-type Ca2+ channels by curcumin requires a novel protein kinase-theta isoform in rat hippocampal neurons

Liu, Kangyong; Gui, Bo; Sun, Yinyi; Shi, Nan; Gu, Zhaohua; Zhang, Ting; Sun, Xiaojiang

doi:10.1016/j.ceca.2012.11.014

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…In addition, studies have shown that Gq and PKC are involved in the inhibition of L-type calcium channels in response to the stimulation of other G-protein coupled receptors. [22][23][24] Thus, to determine whether PKC activation was required to reduce I Ca during sst 4 stimulation, isolated RGCs were pretreated with the PKC antagonist GF109203X (GFX). First, isolated RGCs were incubated with a moderate concentration of GFX (1 mM, 30 min.)…”

Section: Resultsmentioning

confidence: 99%

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

et al. 2014

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Somatostatin subtype-4 receptors (sst4) inhibit L-type calcium channel currents (ICa) in retinal ganglion cells (RGCs). Here we identify the signaling pathways involved in sst4 stimulation leading to suppression of ICa in RGCs. Whole cell patch clamp recordings were made on isolated immunopanned RGCs using barium as a charge carrier to isolate ICa. Application of the selective sst4 agonist, L-803 (10 nM), reduced ICa by 41.2%. Pretreatment of cells with pertussis toxin (Gi/o inhibitor) did not prevent the action of L-803, which reduced ICa by 34.7%. To determine the involvement of Gβγ subunits after sst4 activation, depolarizing pre-pulse facilitation paradigms were used to remove voltage-dependent inhibition of calcium channels. Pre-pulse facilitation did not reverse the inhibitory effects of L-803 on ICa (8.4 vs. 8.8% reductions, ctrl vs. L-803); however, pharmacologic inhibition of Gβγ reduced ICa suppression by L-803 (23.0%, P < 0.05). Inhibition of PKC (GF109203X; GFX) showed a concentration-dependent effect in preventing the action of L-803 on ICa (1 μM GFX, 34.3%; 5 μM GFX, 14.6%, P < 0.05). When both PKC and Gβγ were inhibited, the effects of L-803 on ICa were blocked (1.8%, P < 0.05). These results suggest that sst4 stimulation modulates RGC calcium channels via Gβγ and PKC activation. Since reducing intracellular Ca(2+) is known to be neuroprotective in RGCs, modulating these sst4 signaling pathways may provide insights to the discovery of unique therapeutic targets to reduce intracellular Ca(2+) levels in RGCs.

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Section: Resultsmentioning

confidence: 99%

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

et al. 2014

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“…1, B and C, regulation of a7-nACh receptor function by curcumin occurs gradually, reaching steady-state levels within a few minutes of curcumin application. Therefore, it is possible that activation of second messenger pathways by G-protein-coupled receptors (Pérez-Lara et al, 2011;Liu et al, 2013;Yang et al, 2015) is involved in curcumin regulation of a 7 -nACh receptors. Thus, we investigated the effects of pretreatments with NEM (10 mM, 50 nl, 30-minute preincubation time), a sulfhydryl-alkylating agent that blocks G-protein-effector interactions by alkylating a-subunits of PTX-sensitive GTP binding protein (Oz and Renaud, 2002), and GDPbS (10 mM, 50 nl, 30-minute preincubation time), an agent that inhibits binding of GTP to the a-subunit of G-proteins (Oz et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

Curcumin Acts as a Positive Allosteric Modulator of α₇-Nicotinic Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory Pain

Nebrisi

Bağdaş

Toma

et al. 2018

J Pharmacol Exp Ther

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Effects of curcumin, a major ingredient of turmeric, were tested on the function of the -subunit of the human nicotinic acetylcholine (-nACh) receptor expressed in oocytes and on nociception in mouse models of tonic and visceral pain. Curcumin caused a significant potentiation of currents induced by acetylcholine (ACh; 100M) with an EC value of 0.2 M. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca-dependent Cl channels expressed endogenously in oocytes. Importantly, the extent of curcumin potentiation was enhanced significantly by decreasing ACh concentrations. Curcumin did not alter specific binding of [I]-bungarotoxin. In addition, curcumin attenuated nociceptive behavior in both tonic and visceral pain models without affecting motor and locomotor activity and without producing tolerance. Pharmacological and genetic approaches revealed that the antinociceptive effect of curcumin was mediated by -nACh receptors. Curcumin potentiated the antinociceptive effects of the-nACh receptor agonist -(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU282987). Collectively, our results indicate that curcumin is a positive allosteric modulator of-nACh receptor and reverses nociception in mouse models of tonic and visceral pain.

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“…Calcium channel blockade is one approach among the neuroprotective strategies (Singer, 2012). Curcumin has been demonstrated to reversibly inhibit HVGCC currents via a novel protein kinase C-θ -dependent pathway, which could contribute to its neuroprotective effects in rat hippocampal neurons (Liu et al, 2013). In another study, it has been shown that curcumin inhibits glutamate release from rat prefrontocortical synaptosomes by suppressing presynaptic voltage-gated calcium channels Cav2.2 and Cav2.1 (Lin et al, 2011).…”

Section: Effects Of Curcumin On Ion Channelsmentioning

confidence: 99%

Effects of curcumin on ion channels and transporters

et al. 2014

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Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a polyphenolic compound isolated from the rhizomes of Curcuma longa (turmeric), has been shown to exhibit a wide range of pharmacological activities including anti-inflammatory, anti-cancer, anti-oxidant, anti-atherosclerotic, anti-microbial, and wound healing effects. These activities of curcumin are based on its complex molecular structure and chemical features, as well as its ability to interact with multiple signaling molecules. The ability of curcumin to regulate ion channels and transporters was recognized a decade ago. The cystic fibrosis transmembrane conductance regulator (CFTR) is a well-studied ion channel target of curcumin. During the process of studying its anti-cancer properties, curcumin was found to inhibit ATP-binding cassette (ABC) family members including ABCA1, ABCB1, ABCC1, and ABCG2. Recent studies have revealed that many channels and transporters are modulated by curcumin, such as voltage-gated potassium (Kv) channels, high-voltage-gated Ca2+ channels (HVGCC), volume-regulated anion channel (VRAC), Ca2+ release-activated Ca2+ channel (CRAC), aquaporin-4 (AQP-4), glucose transporters, etc., In this review, we aim to provide an overview of the interactions of curcumin with different types of ion channels and transporters and to help better understand and integrate the underlying molecular mechanisms of the multiple pharmacological activities of curcumin.

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Inhibition of L-type Ca2+ channels by curcumin requires a novel protein kinase-theta isoform in rat hippocampal neurons

Cited by 8 publications

References 34 publications

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

Curcumin Acts as a Positive Allosteric Modulator of α₇-Nicotinic Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory Pain

Effects of curcumin on ion channels and transporters

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Inhibition of L-type Ca2+ channels by curcumin requires a novel protein kinase-theta isoform in rat hippocampal neurons

Cited by 8 publications

References 34 publications

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

Curcumin Acts as a Positive Allosteric Modulator of α7-Nicotinic Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory Pain

Effects of curcumin on ion channels and transporters

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Curcumin Acts as a Positive Allosteric Modulator of α₇-Nicotinic Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory Pain