Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8

Abe, Jiro; Hosokawa, Hiroshi; Sawada, Yosuke; Matsumura, Kiyoshi; Kobayashi, Shígeo

doi:10.1016/j.neulet.2005.12.005

Cited by 91 publications

(87 citation statements)

References 16 publications

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“…TRPM8 is, however, also produced in a range of tissues that are unlikely to be regulated by temperature, including sensory neurons (41) and the malignant prostate (42). The mechanism by which TRPM8 activity is regulated in these tissues remains to be fully determined; however, several regulatory mediators have been identified, including Ca 2+ , pH, PIP2 and phosphorylation (43)(44)(45)(46)(47). In those tissues where CRISP4 and TRPM8 are coexpressed (33), our data suggests that CRISP4 is also likely to modulate TRPM8 function.…”

Section: E)mentioning

confidence: 74%

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Gibbs¹,

Orta

Reddy³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

100

110

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The cysteine-rich secretory proteins (CRISPs) are a group of four proteins in the mouse that are expressed abundantly in the male reproductive tract, and to a lesser extent in other tissues. Analysis of reptile CRISPs and mouse CRISP2 has shown that CRISPs can regulate cellular homeostasis via ion channels. With the exception of the ability of CRISP2 to regulate ryanodine receptors, the in vivo targets of mammalian CRISPs function are unknown. In this study, we have characterized the ion channel regulatory activity of epididymal CRISP4 using electrophysiology, cell assays, and mouse models. Through patch-clamping of testicular sperm, the CRISP4 CRISP domain was shown to inhibit the transient receptor potential (TRP) ion channel TRPM8. These data were confirmed using a stably transfected CHO cell line. TRPM8 is a major cold receptor in the body, but is found in other tissues, including the testis and on the tail and head of mouse and human sperm. Functional assays using sperm from wild-type mice showed that TRPM8 activation significantly reduced the number of sperm undergoing the progesteroneinduced acrosome reaction following capacitation, and that this response was reversed by the coaddition of CRISP4. In accordance, sperm from Crisp4 null mice had a compromised ability to undergo to the progesterone-induced acrosome reaction. Collectively, these data identify CRISP4 as an endogenous regulator of TRPM8 with a role in normal sperm function.cysteine-rich secretory proteins | antigen 5 | pathogenesis-related 1 | epididymal maturation | fertility

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Section: E)mentioning

confidence: 74%

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Gibbs¹,

Orta

Reddy³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

100

110

View full text Add to dashboard Cite

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“…Activation of G proteincoupled receptors (GPCRs) that stimulate phospholipase C (PLC) by a variety of inflammatory mediators such as bradykinin and nerve growth factor (NGF) leads to a diminished cold sensitivity of TRPM8 (Premkumar et al 2005;Abe et al 2006). The effect is mediated by protein kinase C (PKC) and the downstream activation of a protein phosphatase (Premkumar et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Babeș

2009

Biophys Rev

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Substantial progress in understanding thermal transduction in peripheral sensory nerve endings was achieved with the recent cloning of six thermally gated ion channels from the TRP (transient receptor potential) super-family. Two of these channels, TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1), are expressed in dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons, are activated by various degrees of cooling, and are candidates for mediating gentle cooling and noxious cold, respectively. However, accumulating evidence suggests that more than just these two channels are involved in cold sensing in mammals. A recent report described a critical role of the voltage-gated tetrodotoxin-resistant sodium channel Na v 1.8 in perceiving intense cold and noxious stimuli at cold temperatures. Other ion channels, such as two-pore domain background potassium channels (K2P), are known to be expressed in peripheral nerves, have pronounced temperature dependence, and may contribute to cold sensing and/or cold hypersensitivity in pain states. This article reviews the evidence supporting a role for each of these channels in cold transduction, focusing on their biophysical properties, expression pattern, and modulation by pro-inflammatory mediators.

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“…Down-regulation of TRPM8 by the ␣2-adrenoreceptor-coupled Gi/AC/cAMP/ PKA cascade may underlie the analgesic effect of ␣2-adrenoreceptor agonists in TRPM8 overexpression-evoked cold allodynia (37). Ca 2ϩ -induced PKC-dependent phosphorylation has been shown to be indirectly involved in Ca 2ϩ -mediated TRPM8 desensitization (21,22). The latter was also attributed to the depletion of positive TRPM8 modulator, PIP 2 , by the activity of Ca 2ϩ -sensitive PLC␦ (16).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with its quite broad expression, TRPM8 function appears to be regulated not only by cooling temperatures and exogenous chemical imitators of cold, but also by a number of second messengers, which are generated during activation of surface receptor-coupled signaling pathways. Among them is the substrate of phospholipase C (PLC) catalytic activity, phosphatidylinositol bisphosphate (PIP 2 ) (15,16), the products of catalytic activity of Ca 2ϩ -independent subtype of phospholipase A2 (iPLA2), lysophospholipids (LPLs) (17,18), the factors affecting cAMP/protein kinase A (PKA)-dependent phosphorylation (19,20) as well as intracellular Ca 2ϩ ([Ca 2ϩ ] i ) acting either via Ca 2ϩ -sensitive PLC␦ (16) or PKC (21,22). It was also shown that TRPM8 can be directly inhibited by polyunsaturated fatty acids, including the important lipid second messenger arachidonic acid (AA) (17).…”

mentioning

confidence: 99%

Complex Regulation of the TRPM8 Cold Receptor Channel

Bavencoffe

Kondratskyi

Gkika

et al. 2011

Journal of Biological Chemistry

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Cold/menthol-activated TRPM8 (transient receptor potential channel melastatin member 8) is primarily expressed in sensory neurons, where it constitutes the principal receptor of environmental innocuous cold. TRPM8 has been shown to be regulated by multiple influences such as phosphorylation, pH, Ca 2؉ , and lipid messengers. One such messenger is arachidonic acid (AA), which has been shown to inhibit TRPM8 channel activity. However, the physiological pathways mediating the inhibitory effect of AA on TRPM8 still remain unknown. Here, we demonstrate that TRPM8 is regulated via M3 muscarinic acetylcholine receptor-coupled signaling cascade based on the activation of cytosolic phospholipase A2 (cPLA2) and cPLA2-catalyzed derivation of AA. Stimulation of M3 receptors heterologously co-expressed with TRPM8 in HEK-293 cells by nonselective muscarinic agonist, oxotremorine methiodide (Oxo-M), caused inhibition of TRPM8-mediated membrane current, which could be mimicked by AA and antagonized by pharmacological or siRNA-mediated cPLA2 silencing. Our results demonstrate the intracellular functional link between M3 receptor and TRPM8 channel via cPLA2/AA and suggest a novel physiological mechanism of arachidonate-mediated regulation of TRPM8 channel activity through muscarinic receptors. We also summarize the existing TRPM8 regulations and discuss their physiological and pathological significance.The members of the transient receptor potential (TRP) 5 superfamily of cationic channels display extraordinary diverse activation mechanisms and participate in the plethora of physiological and pathological processes (1), which made them the focus of intense research over the last decades. A number of TRPs, dubbed thermo-TRPs, from TRPV (vanilloid), TRPM (melastatin), and TRPA (ankyrin) subfamilies can be activated by various ambient temperatures ranging from noxious cold to noxious heat. They also respond to the chemical imitators of temperatures of various modalities and to the number of chemical and environmental irritants (2). Among them, TRPM8, which is activated by innocuous cold (Ͻ25°C) (3) and a well known cooling agent, peppermint oil component, menthol, represents a cold receptor. Except for the innocuous cold and menthol, TRPM8 can also be activated by some other cooling agents such as icilin and eucalyptol as well as by noncooling compounds hydroxy-citronellal, geraniol, and linalool (4). It has been shown that the mechanism of TRPM8 activation by cold and menthol involves negative shift in the voltage-dependent opening of the channel from very positive unphysiological membrane potentials toward physiological values (5, 6).Despite being proven as the principal detector of environmental cold (7-9), TRPM8 expression is by far not limited to the subset of cold-sensitive dorsal root ganglion and trigeminal sensory neurons in which it functions as cold-activated receptor channel. In fact, sizable TRPM8 expression was found in prostate (10), sperm (11), some epithelial (12, 13), and smooth muscle (14) cells as well as in canc...

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Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8

Cited by 91 publications

References 16 publications

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Complex Regulation of the TRPM8 Cold Receptor Channel

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