Herbicideacetochlorinhibitsadrenergicreceptor-mediatedcalciumoscillationsinrathepatocytesLIUFangyuan1)ZHANGBinbin1,2)CUIZongjie1)†(1)InstituteofCellBiology,BeijingNormalUniversity,100875,Beijing,China;2)CenterforBiotechnologyExperimentalTeaching,SchoolofPharmacy,BinzhouMedicalUniversity,264003,Yantai,Shandong,China)AbstractHerbicideacetochlorafterapplicationentersbothsurfaceandundergroundwaters,sothatacetochlorconcentrationsinriversandstreamscouldbesufficientlyhigh(nmol·L−1)toexertlong-termeffectsinaquaticanimals.Occupationalexposuremayposegreaterrisksduetoskinandinhalationexposures,resultinginmuchhighertransientbloodacetochlorconcentrations(μmol·L−1).Previousworkshaveidentifiedliverasthemostsusceptibletoxicologicaltargetforacetochlor,andcytosoliccalciumisknowntoplayavitalroleinmultiplehepatocytefunctions.Thereforethepresentworkaimstoexamineacetochloreffectoncalciumoscillationsinducedbyadrenergicreceptoractivationinfreshlyisolatedrathepatocytes.Itwasfoundthatacetochloratlowerconcentrations(1,10μmol·L−1)addedsimultaneouslywithphenylepinephrine(PE)hadnoeffectonPE-inducedcalciumoscillations,butinhibitedreversiblycalciumoscillationsathigherdoses(50,100,200μmol·L−1)ofacetochlorinselectedhepatocytes.Briefprioracetochlorexposure(1,10,100μmol·L−1),however,hadnoapparenteffectoneitherbasalcalciumorsubsequentPE-inducedcalciumoscillations.Immunocytochemistryidentifiednon-uniformα1adrenergicreceptorexpressionamongisolatedhepatocytes.Immunohistochemistryofliverslicesrevealedadistinctpatternofα1adrenergicreceptordensityinliverlobules:agraduallow-to-highreceptordensitygradientfrompericentraltoperiportalregions.Thisreceptordensitygradientislikelyrelatedtoacetochlorinhibitioninselectedhepatocytes.Takentogetheritisconcludedthatacetochloratbloodconcentrationsattainableduringacuteskinexposureoracetochlorpoisoningmayexerttransientinhibitoryeffectsonα1receptorsignalingintheliver.Keywordsacetochlor;adrenergicreceptor;calciumo...