Waglerin-1(Wtx-1) isapeptideoriginallyisolatedfromthevenomoftheWagler’spitviper(Trimeresuruswagleri).This22amino-acidpeptideisacompetitiveantagoNISTofmusclenicotinicacetylcholinereceptors. Waglerin-1competeswithα-bungarotoxin.
Waglerin-1 isaninterestingtooltodiscriminatebetweenfetalandadultmusclenAChRsasitbindstotheα-εsubunitinterfacewitha~2000foldhigheraffinitythantotheα-γorα-δsubunits.Waglerin-1isknowntobind100foldmorepotentlytonAChRfromadultmicethanthatfromratorhumans.ItblocksmusclenAChRfromadultmicewithanIC50valueof50nM.
Somestudieshavedemonstratedthat Waglerin-1 hasaneffectonionotropicGABAreceptors.ItmaypotentiateordepressI(GABA)dependingontheneurons.
Somederivativesof Waglerin-1 arecurrentlyusedincosmeticstoreducewrinkles.
Description:
AAsequence: Gly-Gly-Lys-Pro-Asp-Leu-Arg-Pro-Cys9-His-Pro-Pro-Cys13-His-Tyr-Ile-Pro-Arg-Pro-Lys-Pro-Arg-OH
Disulfidebonds: Cys9-Cys13
Length(aa): 22
Formula: C112H175N37O26S2
MolecularWeight: 2520Da
Appearance: Whitelyophilizedsolid
Solubility: waterorsalinebuffer
CASnumber: NA
Source: Synthetic
Reference:
Peptide-toxintoolsforprobingtheexpressionandfunctionoffetalandadultsubtypesofthenicotinicacetylcholinereceptor
Althoughtheneuromuscularnicotinicacetylcholinereceptor(nAChR)isoneofthemostintensivelystudiedionchannelsinthenervoussystem,thedifferentialrolesoffetalandadultsubtypesofthenAChRundernormalandpathologicalconditionsarestillincompletelydefined.Untilrecently,nopharmacologicaltoolsdistinguishedbetweenfetalandadultsubtypes.Waglerintoxins(fromsnakevenom)&alphaA(S)-conotoxins(fromcone-snailvenom)haveprovidedsuchtools.Becausethesepeptideswerecharacterizedbydifferentresearchgroupsusingdifferentmethods,wehave:1)moreextensivelytestedtheirsubtypeselectivity,and2)beguntoexplorehowthesepeptidesmaybeusedinconcerttoelucidateexpressionpatternsandfunctionsoffetalandadultnAChRs.Inheterologousexpressionsystemsandnativetissues,Waglerin-1&analphaA(S)-conotoxinanalog,alphaA-OIVA[K15N],arehigh-affinity,highlyselectiveinhibitorsoftheadultandfetalmusclenAChRs,respectively.WehaveusedthepeptidesandtheirfluorescentderivativestoexploretheexpressionandfunctionofthefetalandadultnAChRsubtypes.WhilefluorescentderivativesofthesepeptidesindicatedagradualtransitionfromfetaltoadultmusclenAChRsinmiceduringthefirst2weekspostnatal,weunexpectedlyobservedasteepertransitioninfunctionalexpressioninthemousediaphragmmuscleusingelectrophysiology.Asatoolkitofpharmacologicalagentswithcomplementaryspecificity,alphaA-OIVA[K15N]&Waglerin-1shouldhavefurtherutilityindeterminingtherolesoffetal&adultnAChRsubtypesindevelopment,inmaturetissues,andunderpathologicalconditions.
TeichertRW. etal. Peptide-toxintoolsforprobingtheexpressionandfunctionoffetalandadultsubtypesofthenicotinicacetylcholinereceptor. AnnNYAcadSci. PMID: 18567854
ConformationalanalysisofatoxicpeptidefromTrimeresuruswagleriwhichblocksthenicotinicacetylcholinereceptor
SellinLC. etal. ConformationalanalysisofatoxicpeptidefromTrimeresuruswagleriwhichblocksthenicotinicacetylcholinereceptor. BiophysJ. 1996. PMID: 8770182
IdentificationofresiduesatthealphaandepsilonsubunitinterfacesmediatingspeciesselectivityofWaglerin-1fornicotinicacetylcholinereceptors
MollesBE. etal. IdentificationofresiduesatthealphaandepsilonsubunitinterfacesmediatingspeciesselectivityofWaglerin-1fornicotinicacetylcholinereceptors. JBiolChem.2002. PMID: 11724791
Waglerin-1selectivelyblockstheepsilonformofthemusclenicotinicacetylcholinereceptor
McArdleJJ. etal.Waglerin-1selectivelyblockstheepsilonformofthemusclenicotinicacetylcholinereceptor. JPharmacolExpTher. PMID: 10087048
Waglerin-1inhibitsGABA(A)currentofneuronsinthenucleusaccumbensofneonatalrats.BrainRes
TheeffectofWaglerin-1,a22-aminoacidpeptidepurifiedfromthevenomofWagler’spitviperonthewholecellcurrentresponse(I(GABA))togamma-aminobutyricacid(GABA)wasexaminedforneuronsfreshlyisolatedfromthenucleusaccumbensof3-to7-day-oldrats.Waglerin-1depressedI(GABA)inducedbysubsaturatingconcentrationsofGABA;theIC(50)forI(GABA)inducedby10microMGABAwas2.5microMWaglerin-1.ThisconcentrationofWaglerin-1shiftedtheGABAconcentration-responsecurvetotherightinaparallelmanner,increasingtheGABAEC(50)from12+/-3to27+/-5microM.ThedepressanteffectofWaglerin-1wasgreateratnegativeholdingpotentials.Zn(2+)alsoinhibitedI(GABA)withanIC(50)of0.3microM.PhosphorylationstateappearedtomodulateGABA(A)receptorsensitivitytotheinhibitoryeffectofWaglerin-1sincedialysisofneuronswithN-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamideHCl(H-89),aninhibitorofproteinkinaseA,preventedinhibition.ThedataarediscussedintermsofdevelopmentalinfluencesonthesubunitcompositionofGABA(A)receptorsinneuronsofthenucleusaccumbens.
YeJH. etal. Waglerin-1inhibitsGABA(A)currentofneuronsinthenucleusaccumbensofneonatalrats. BrainRes. 1999. PMID: 10433985
Waglerin-1modulatesgamma-aminobutyricacidactivatedcurrentofmurinehypothalamicneurons
YeJH. etal.Waglerin-1modulatesgamma-aminobutyricacidactivatedcurrentofmurinehypothalamicneurons. JPharmacolExpTher. PMID: 9223541 Smartox生物素ProTx-I电压门控钠通道和T型Cav的阻断剂毒素I（ProTx-1；β-theraphotoxin-Tp1a） 是一种毒素，最初是从Prixopelma pruriens（秘鲁绿色天鹅绒狼蛛）的毒液中分离出来的。此毒素可逆地抑制抗河豚毒素（TTX）的通道 Na v 1.8（IC 50 = 27 nM）和 Na v 1.2，Na v 1.5和Na v 1.7 ，IC 50 值为50至100 nM。此外， ProTx-I 改变了T型Ca v 3.1通道的电压依赖性活动 （IC 50 = 50 nM），而不会影响灭活的电压依赖性。生物素ProTx-I是ProTx-I的生物素标签版本。
