除草剂乙草胺抑制大鼠肝脏细...所介导的胞浆钙振荡（英文）_刘方圆.pdf

Herbicide acetochlor inhibits adrenergic receptor-mediatedcalcium oscillations in rat hepatocytesLIUFangyuan1）ZHANGBinbin1，2）CUIZongjie1）（1）InstituteofCellBiology，BeijingNormalUniversity，100875，Beijing，China；2）CenterforBiotechnologyExperimentalTeaching，SchoolofPharmacy，BinzhouMedicalUniversity，264003，Yantai，Shandong，China）AbstractHerbicideacetochlorafterapplicationentersbothsurfaceandundergroundwaters，sothatacetochlorconcentrationsinriversandstreamscouldbesufficientlyhigh（nmolL1）toexertlong-termeffectsinaquaticanimals.Occupationalexposuremayposegreaterrisksduetoskinandinhalationexposures，resultinginmuchhighertransientbloodacetochlorconcentrations（molL1）.Previousworkshaveidentifiedliverasthemostsusceptibletoxicologicaltargetforacetochlor，andcytosoliccalciumisknowntoplayavitalroleinmultiplehepatocytefunctions.Thereforethepresentworkaimstoexamineacetochloreffectoncalciumoscillationsinducedbyadrenergicreceptoractivationinfreshlyisolatedrathepatocytes.Itwasfoundthatacetochloratlowerconcentrations（1，10molL1）addedsimultaneouslywithphenylepinephrine（PE）hadnoeffectonPE-inducedcalciumoscillations，butinhibitedreversiblycalciumoscillationsathigherdoses（50，100，200molL1）ofacetochlorinselectedhepatocytes.Briefprior acetochlor exposure（1，10，100 molL1），however，had no apparent effect on either basal calcium orsubsequent PE-induced calcium oscillations.Immunocytochemistry identified non-uniform 1 adrenergic receptorexpression among isolated hepatocytes.Immunohistochemistry of liver slices revealed a distinct pattern of 1adrenergic receptor density in liver lobules:a gradual low-to-high receptor density gradient from pericentral toperiportalregions.Thisreceptordensitygradientislikelyrelatedtoacetochlorinhibitioninselectedhepatocytes.Taken together it is concluded that acetochlor at blood concentrations attainable during acute skin exposure oracetochlorpoisoningmayexerttransientinhibitoryeffectson1receptorsignalingintheliver.Keywordsacetochlor；adrenergicreceptor；calciumoscillations；hepatocytesDOI：10.12202/j.0476-0301.2022145 0 IntroductionPesticides are widely used to prevent loss inagricultural production.A sizable portion of agriculturalpesticidesusedareherbicides，includingchloroacetanilideherbicides such as acetochlor1.Annual acetochlor usebothinindustrializedUSandindevelopingChinaisinthetensofmillionsofpounds24.Acetochlor has high water solubility，low soiladsorption，thereforeiseasilytransportedfromfarmfieldsbysurfacerunoff56.Acetochlorconcentrationsinsurfacewaters have been found to be in the nanomolar range:0.926nmolL17，0.63nmolL18，1.11nmolL19，2.85nmolL110，9.3nmolL111，0.192.67nmolL112，6.15 nmolL113，3.91 nmolL1（1054.90ngL1）14.Atmosphericacetochlorhasalsobeendetec-ted，valuesofupto53.5ngm3（198.15nmolL1）hasbeen found15.Acetochlor concentration in the rain-waterthereforecouldbeupto9.27nmolL116，16.26nmolL117.Duetoitshighsoilmobility，thepresenceof acetochlor in soil has been found to be rathertransient1820.Acetochlorsoilrunoffintosurfacewaterandinfiltrationtoundergroundwater，aerosolizedacetochlorprecipitatedinrainwater，togetherformcriticalroutesofCorrespondingauthor:CUIZongjie，E-mail:Dateofreceipt:2022-05-052023-02北京师范大学学报（自然科学版）59（1）JournalofBeijingNormalUniversity（NaturalScience）43acetochlordispersionbeforemovingintotheocean18，2122.Compared with acetochlor in the environment，occupationalexposuretoacetochlorposesgreaterharmtohumanhealth.Acetachlormetabolitesarereadilydetectedin the urine of farmers23 and farm children24，withseasonal variations23，25.Urine acetochlor up to 0.26nmolL1hasbeendetectedinpregnantwomenresidingclose to fields of acetochlor application26.Prenatalexposure to acetochlor and other herbicides has beencorrelatedtoreducedbirthweightinhumaninfants2728.The effect of long-term and chronic exposure tonanomolaracetochlorhasbeenextensivelyinvestigated.Ithas been found that exposure to environmental concen-trationsofacetochlorincreasedthyroidhormonereceptorexpressioninaquaticanimals2931.Acetochlor-spikedfeedincreased estrogen receptor density in the rat3233.Acetochlor accelerated frog tadpole metamorphosis viaincreasedexpressionofthethyroidhormonereceptor3435.Long-term low level acetochlor exposure notwith-standing，effect of short-term occupational exposure athigher concentration has been less well studied.Micro-molaracetochlorconcentrationshavebeenreportedintheserumofacutelypoisonedpatients（18.61molL1）36，in skin-exposed monkeys（0.37 molL1）37.Further，humanskinexposure（at9.27mmolL1）couldleadtocontactdermatitis38.Thereforethepresentworkaimstoexamineacetochloreffectoncalciumsignalinthefreshlyisolatedrathepatocytes.Sincethe1adrenergicreceptorplaysaprominentroleincalciumsignalinginhepatocytes3943，acetochloreffectonadrenergicreceptor-mediatedcalciumoscillationswasexamined.ItwasfoundthatmicromolaracetochlorshowedreversibleinhibitionofPE-induced cytoslic calcium oscillations in hepatocytes.Duetotheuniversalroleofcalciumsignalinginmultiplecell types，this new finding has potentially importantbearings on the occupational health