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- Bertrand,D. etal. (1990) Proc.Natl.Acad.Sci.U.S.A. 87, 1993.
- AlomoneLabs1,1-Dimethyl-4-phenylpiperaziniumiodideactivatesmusclefetalα1/β1/γ/δnAChRheterologouslyexpressedin Xenopus oocytes.A.TimecourseofcurrentrepetitiveandreversIBLeactivationby100µM 1,1-Dimethyl-4-phenylpiperaziniumiodide (#D-125).Holdingpotentialwas-60mVandcurrentswereelicitedbyapplicationof100µMacetylcholine.B.Exampletracesofcurrentresponsesto10mMor100mMacetylcholineasindicated.
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Nicotinicacetylcholinereceptors(nAChRs)areligand-gatedionchannelscomprisingfivesubunits.Themuscle-typereceptorismadeoftwoα1,β,γandδsubunits,whiletheneuronalnicotinicreceptorsareformedbydifferentcombinationsoftwoαandthreeβsubunits.Thesereceptorsareexpressedonneuronalanddifferenttypesofnon-neuronalcellssuchas,lymphocytes,alveolarmacrophages,airwaysmoothmusclecells,epithelialcells,andfibroblasts1.
nAChRsmediatenumerousspecificphysiologicalfunctionsdependingonthetypeofcellinvolved.Forexample,nicotineinducesthereleaseofdopamineinthecentralnervoussystemandstimulatesnitricoxide(NO)synthasegeneexpressioninendothelialcells2.
1,1-Dimethyl-4-phenylpiperaziniumiodide(DMPP)isaselectivenAChRagoNIST.Foralongtime,DMPPwasconsideredtobetheprototypeofganglionicstimulatingagent,sinceitwasabletoactivatethenicotinicreceptorinsympatheticgangliawithhigherpotencythanthemuscle-type.However,ithassincebeenshownthatDMPPbindswithhigheraffinitytothenicotinicreceptorinthebrain3.DMPPactivatesα4nicotinicchannelsexpressedin Xenopus oocyteswithIC50of0.77uM4.
Nicotinicagonists,suchasDMPP,haveanti-inflammatoryeffectsinmousemodelsofhypersensitivitypneumonitis,asthma,airwayinflammation,andTypeIdiabetes5.DMPPreducesthereleaseofIL-1andTNFfromisolatedspleencells,andthereleaseofTNFandIL-6frommacrophages6.
1,1-Dimethyl-4-phenylpiperaziniumiodide(#D-125) isahighlypure,synthetic,andbiologicallyactivecompound.