1、Herbicide acetochlor inhibits adrenergic receptor-mediatedcalcium oscillations in rat hepatocytesLIUFangyuan1)ZHANGBinbin1,2)CUIZongjie1)(1)InstituteofCellBiology,BeijingNormalUniversity,100875,Beijing,China;2)CenterforBiotechnologyExperimentalTeaching,SchoolofPharmacy,BinzhouMedicalUniversity,26400
2、3,Yantai,Shandong,China)AbstractHerbicideacetochlorafterapplicationentersbothsurfaceandundergroundwaters,sothatacetochlorconcentrationsinriversandstreamscouldbesufficientlyhigh(nmolL1)toexertlong-termeffectsinaquaticanimals.Occupationalexposuremayposegreaterrisksduetoskinandinhalationexposures,resul
3、tinginmuchhighertransientbloodacetochlorconcentrations(molL1).Previousworkshaveidentifiedliverasthemostsusceptibletoxicologicaltargetforacetochlor,andcytosoliccalciumisknowntoplayavitalroleinmultiplehepatocytefunctions.Thereforethepresentworkaimstoexamineacetochloreffectoncalciumoscillationsinducedb
4、yadrenergicreceptoractivationinfreshlyisolatedrathepatocytes.Itwasfoundthatacetochloratlowerconcentrations(1,10molL1)addedsimultaneouslywithphenylepinephrine(PE)hadnoeffectonPE-inducedcalciumoscillations,butinhibitedreversiblycalciumoscillationsathigherdoses(50,100,200molL1)ofacetochlorinselectedhep
5、atocytes.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 revea
6、led 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 c
7、oncentrations attainable during acute skin exposure oracetochlorpoisoningmayexerttransientinhibitoryeffectson1receptorsignalingintheliver.Keywordsacetochlor;adrenergicreceptor;calciumoscillations;hepatocytesDOI:10.12202/j.0476-0301.2022145 0 IntroductionPesticides are widely used to prevent loss ina
8、gricultural production.A sizable portion of agriculturalpesticidesusedareherbicides,includingchloroacetanilideherbicides such as acetochlor1.Annual acetochlor usebothinindustrializedUSandindevelopingChinaisinthetensofmillionsofpounds24.Acetochlor has high water solubility,low soiladsorption,therefor
9、eiseasilytransportedfromfarmfieldsbysurfacerunoff56.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,v
10、aluesofupto53.5ngm3(198.15nmolL1)hasbeen found15.Acetochlor concentration in the rain-waterthereforecouldbeupto9.27nmolL116,16.26nmolL117.Duetoitshighsoilmobility,thepresenceof acetochlor in soil has been found to be rathertransient1820.Acetochlorsoilrunoffintosurfacewaterandinfiltrationtoundergroun
11、dwater,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 t
12、he environment,occupationalexposuretoacetochlorposesgreaterharmtohumanhealth.Acetachlormetabolitesarereadilydetectedin the urine of farmers23 and farm children24,withseasonal variations23,25.Urine acetochlor up to 0.26nmolL1hasbeendetectedinpregnantwomenresidingclose to fields of acetochlor applicat
13、ion26.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-trationsofacetochlorincreasedthyr
14、oidhormonereceptorexpressioninaquaticanimals2931.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-te
15、rm 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.Thereforethepres
16、entworkaimstoexamineacetochloreffectoncalciumsignalinthefreshlyisolatedrathepatocytes.Sincethe1adrenergicreceptorplaysaprominentroleincalciumsignalinginhepatocytes3943,acetochloreffectonadrenergicreceptor-mediatedcalciumoscillationswasexamined.ItwasfoundthatmicromolaracetochlorshowedreversibleinhibitionofPE-induced cytoslic calcium oscillations in hepatocytes.Duetotheuniversalroleofcalciumsignalinginmultiplecell types,this new finding has potentially importantbearings on the occupational health