TAILIEUCHUNG - Báo cáo khoa học: Biochemical pharmacology of the vanilloid receptor TRPV1 An update

There is mounting evidence that the vanilloid (capsaicin) receptor; transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), is subjected to multiple interacting levels of control. The first level is by reversible phosphorylation catalyzed by intrinsic kinases (. protein kinase A and C) and phosphatases (. calcineurin), which plays a pivotal role in receptor sensitization vs. tachyphy-laxis. In addition, this mechanism links TRPV1 to intracel-lular signaling by various important endogenous as well as exogenous substances such as bradykinin, ethanol, nicotin and insulin | Eur. J. Biochem. 271 1814-1819 2004 FEBS 2004 doi MINIREVIEW Biochemical pharmacology of the vanilloid receptor TRPV1 An update Daniel N. Cortright1 and Arpad Szallasi2 1Neurogen Corporation Branford CT USA department of Pathology and Laboratory Medicine University of Pennsylvania Philadelphia PA USA There is mounting evidence that the vanilloid capsaicin receptor transient receptor potential channel vanilloid subfamily member 1 TRPV1 is subjected to multiple interacting levels of control. The first level is by reversible phosphorylation catalyzed by intrinsic kinases . protein kinase A and C and phosphatases . calcineurin which plays a pivotal role in receptor sensitization vs. tachyphylaxis. In addition this mechanism links TRPV1 to intracellular signaling by various important endogenous as well as exogenous substances such as bradykinin ethanol nicotin and insulin. It is not clear however whether phosphorylation per se is sufficient to liberate TRPV1 under the inhibitory control of phosphatydylinositol-4 5-bisphosphate. The second level of control is by forming TRPV1 heteromers and their association with putative regulatory proteins. The next level of regulation is by subcellular compartmentalization. The membrane form of TRPV1 functions as a nonselective cation channel. On the endoplasmic reticulum TRPV1 is present in two differentially regulated forms one of which is inositol triphosphate-dependent whereas the other is not. These three TRPV1 compartments provide a versatile regulation of intracellular Ca2 levels. Last there is a complex and poorly understood regulation of TRPV1 activity via control of gene expression. Factors that down-regulate TRPV1 expression include vanilloid treatment and growth factor notably nerve growth factor deprivation. By contrast TRPV1 appears to be upregulated during inflammatory conditions. Interestingly following experimental nerve injury and in animal models of diabetic neuropathy TRPV1 is

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