Complex regulation of capsaicin on intracellular second messengers by calcium dependent and independent mechanisms in primary sensory neurons

Xu, Yu; Zhang, Jie wen; Li, Li; Zhang, Yi; Gao, Xiang; Li, Fen; Yan, Xi; Liu, Zhi Guo; Liu, Lie ju; Cao, Xue Hong

doi:10.1016/j.neulet.2012.04.011

Cited by 18 publications

(19 citation statements)

References 32 publications

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“…Importantly, readdition of Ca 2ϩ to a final concentration of 1.25 mM resulted in a robust translocation similar to that in Figure 1. We have obtained similar results earlier with menthol and TRPM8 using a fluorescence resonance energy transfer-based approach, monitoring PI(4,5)P 2 with the CFP and YFP tagged PH domains of PLC␦4 (Yudin et al, 2011).…”

Section: Casupporting

confidence: 82%

“…This is not very likely, however, because a large number of wellcharacterized PI(4,5)P 2 dependent ion channels have been shown to be robustly inhibited by this enzyme or its relative C-VSP upon depolarization (Hossain et al, 2008;Suh et al, 2010;Yudin et al, 2011). Similar to D-VSP, we could not detect any inhibition of TRPV1 currents using C-VSP (data not shown).…”

Section: Camentioning

confidence: 70%

“…All animal procedures were approved by the Institutional Animal Care and Use Committee. Dorsal root ganglion (DRG) neurons were isolated from 2-to 4-month-old wild-type C57BL6 or PLC␦4 Ϫ/Ϫ (Fukami et al, 2001) (C57BL6 background) mice as described previously (Yudin et al, 2011) with some modifications. DRG neurons were isolated from mice of either sex anesthetized and perfused via the left ventricle with ice-cold Hank's buffered salt solution (HBSS; Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…Whole-cell patch-clamp recordings were performed at room temperature (22-24°C) as described previously (Yudin et al, 2011). Patch pipettes were pulled from borosilicate glass capillaries (1.75 mm outer diameter, Sutter Instruments) on a P-97 pipette puller (Sutter Instrument) to a resistance of 4 -6 M⍀.…”

Section: Methodsmentioning

confidence: 99%

“…The former releases Ca 2ϩ from internal stores; the latter activates PKC. PI(4,5)P 2 , in its own right, is also a general regulator of many different mammalian ion channels (Logothetis and Nilius, 2007; Suh and Hille, 2008;Gamper and Rohacs, 2012), including TRP channels (Nilius et al, 2008;Rohacs, 2009). TRPV1 was originally proposed to be inhibited by PI(4,5)P 2 (Chuang et al, 2001), but later studies showed that PI(4,5)P 2 chelating agents inhibit capsaicin-induced TRPV1 currents in excised patches while resupplying PI(4,5)P 2 or its precursor PI(4)P to the cytoplasmic leaflet of the patch membrane reactivates the channel (Stein et al, 2006;Lukacs et al, 2007;Klein et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Distinctive Changes in Plasma Membrane Phosphoinositides Underlie Differential Regulation of TRPV1 in Nociceptive Neurons

Lukacs

Yudin

Hammond

et al. 2013

Journal of Neuroscience

158

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Transient Receptor Potential Vanilloid 1 (TRPV1) is a polymodal, Ca 2ϩ-permeable cation channel crucial to regulation of nociceptor responsiveness. Sensitization of TRPV1 by G-protein coupled receptor (GPCR) agonists to its endogenous activators, such as low pH and noxious heat, is a key factor in hyperalgesia during tissue injury as well as pathological pain syndromes. Conversely, chronic pharmacological activation of TRPV1 by capsaicin leads to calcium influx-induced adaptation of the channel. Paradoxically, both conditions entail activation of phospholipase C (PLC) enzymes, which hydrolyze phosphoinositides. We found that in sensory neurons PLC␤ activation by bradykinin led to a moderate decrease in phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ), but no sustained change in the levels of its precursor PI(4)P. Preventing this selective decrease in PI(4,5)P 2 inhibited TRPV1 sensitization, while selectively decreasing PI(4,5)P 2 independently of PLC potentiated the sensitizing effect of protein kinase C (PKC) on the channel, thereby inducing increased TRPV1 responsiveness. Maximal pharmacological TRPV1 stimulation led to a robust decrease of both PI(4,5)P 2 and its precursor PI(4)P in sensory neurons. Attenuating the decrease of either lipid significantly reduced desensitization, and simultaneous reduction of PI(4,5)P 2 and PI(4)P independently of PLC inhibited TRPV1. We found that, on the mRNA level, the dominant highly Ca 2ϩ -sensitive PLC isoform in dorsal root ganglia is PLC␦4. Capsaicin-induced desensitization of TRPV1 currents was significantly reduced, whereas capsaicininduced nerve impulses in the skin-nerve preparation increased in mice lacking this isoform. We propose a comprehensive model in which differential changes in phosphoinositide levels mediated by distinct PLC isoforms result in opposing changes in TRPV1 activity.

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Section: Casupporting

confidence: 82%

Section: Camentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Distinctive Changes in Plasma Membrane Phosphoinositides Underlie Differential Regulation of TRPV1 in Nociceptive Neurons

Lukacs

Yudin

Hammond

et al. 2013

Journal of Neuroscience

158

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Acute Toxicity of Respiratory Irritant Exposures

Miller

2013

The Toxicant Induction of Irritant Asthma, Rhinitis, and Related Conditions

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Capsaicin and Its Role in Chronic Diseases

Fernandes

Cerqueira

Soares

et al. 2016

Advances in Experimental Medicine and Biology

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A significant number of experimental and clinical studies published in peer-reviewed journals have demonstrated promising pharmacological properties of capsaicin in relieving signs and symptoms of non-communicable diseases (chronic diseases). This chapter provides an overview made from basic and clinical research studies of the potential therapeutic effects of capsaicin, loaded in different application forms, such as solution and cream, on chronic diseases (e.g. arthritis, chronic pain, functional gastrointestinal disorders and cancer). In addition to the anti-inflammatory and analgesic properties of capsaicin largely recognized via, mainly, interaction with the TRPV1, the effects of capsaicin on different cell signalling pathways will be further discussed here. The analgesic, anti-inflammatory or apoptotic effects of capsaicin show promising results in arthritis, neuropathic pain, gastrointestinal disorders or cancer, since evidence demonstrates that the oral or local application of capsaicin reduce inflammation and pain in rheumatoid arthritis, promotes gastric protection against ulcer and induces apoptosis of the tumour cells. Sadly, these results have been paralleled by conflicting studies, which indicate that high concentrations of capsaicin are likely to evoke deleterious effects, thus suggesting that capsaicin activates different pathways at different concentrations in both human and rodent tissues. Thus, to establish effective capsaicin doses for chronic conditions, which can be benefited from capsaicin therapeutic effects, is a real challenge that must be pursued.

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Complex regulation of capsaicin on intracellular second messengers by calcium dependent and independent mechanisms in primary sensory neurons

Cited by 18 publications

References 32 publications

Distinctive Changes in Plasma Membrane Phosphoinositides Underlie Differential Regulation of TRPV1 in Nociceptive Neurons

Distinctive Changes in Plasma Membrane Phosphoinositides Underlie Differential Regulation of TRPV1 in Nociceptive Neurons

Acute Toxicity of Respiratory Irritant Exposures

Capsaicin and Its Role in Chronic Diseases

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