tailieunhanh - Báo cáo khoa học: Endovanilloids Putative endogenous ligands of transient receptor potential vanilloid 1 channels

Endovanilloids are defined as endogenous ligands of the transient receptor potential vanilloid type 1 (TRPV1) protein,a nonselective cation channel that belongs to the large family of TRP ion channels,and is activated by the pungent ingredient of hot chilli peppers,capsaicin. TRPV1 is expressed in some nociceptor efferent neurons, where it acts as a molecular sensor of noxious heat and low pH. However,the presence of these channels in var-ious regions of the central nervous system,where they are not likely to be targeted by these noxious stimuli,suggests the existence of endovanilloids. Three different classes of endogenous lipids have been found recently that can activate TRPV1, | Eur. J. Biochem. 271 1 í í -1 i i 4 2004 FEBS 2004 doi MINIREVIEW Endovanilloids Putative endogenous ligands of transient receptor potential vanilloid 1 channels Mario van der Stelt and Vincenzo Di Marzo Endocannabinoid Research Group Istituto di Chimica Biomolecolare Consiglio Nazionale delle Ricerche Pozzuoli Italy Endovanilloids are defined as endogenous ligands of the transient receptor potential vanilloid type 1 TRPV1 protein a nonselcciive caiion channel that belongs to the large family of TRP ion channels ndd is activated yy the pungent ingredient of hot chilli peppers vapcaicin. TRPV1 is expressed in some nociceptor efferent neurons where it acts as a molecular sensor of noxious heat and low pH. However file presenee of timse n nl k in aar-ious regions of the central nervous system where they are not likely to be targeted by these noxious stimuli suggstss the existence of endovanilloids. Three different classes of endogenous lipids have been found recently that can activate TRPV1 . nm tu LI 1 1 1 ir -acyldoamiéntts. -ip-oxygenase products of arachidonic acid and the endo cannabinoid anandamide with some of its congeners. To classify a molecule as an endovanilloid the compound should be formed or released in an activity-dependent manner in sufficient amounts to evoke a TRPV1-mediated response by direct activation of the channel. To control TRPV1 signaling endovanilloids should be inactivated within a short time-span. In this review we will dnsLlss. for each of the proposed endogenous ligands of TRPV1 their ability to act as endovanilloids in light of the criteria mentioned above. Keywords anandamide arachidonic acid cannabinoid lipid signaling TRP VR1. Introduction The transient receptor potential vanilloid type 1 TRPV1 protein is a nonselective cation channel that belongs to the large family of TRP ion channels and is highly expressed in small diameter primary afferent fibers 1 . It is a molecular integrator of noxious .