title: Effect of pirimiphos-methyl on proteolytic enzyme activities in rat heart, kidney, brain and liver tissues in vivo.
abstract: To elucidate whether pesticide toxicity in higher animals involves pesticide-induced dysfunction of the intracellular protein catabolic process, we have determined the effect in vivo of the organophosphate insecticide pirimiphos-methyl on the activities of representative protein catabolising cytoplasmic and lysosomal proteases (responsible for the various stages of the protein degradation cascade and essential for normal cell functioning) in heart, kidney, brain and liver target tissues in the rat. In liver tissue (the major site of pesticide metabolism), the activities of all of the cytoplasmic proteases investigated (alanyl-, arginyl-, leucyl aminopeptidases, dipeptidyl aminopeptidase IV, tripeptidyl aminopeptidase, proline endopeptidase) were significantly inhibited (by 20-40% of control activity) following administration of 10 mg pirimiphos-methyl/kg bodyweight, whereas of the lysosomal proteases investigated, only the activities of dipeptidyl aminopeptidase I and cathepsin D were significantly reduced (by 15-20% of control activity). In contrast, there was no insecticide-induced inhibition of protease activities in heart, kidney or brain tissues; some lysosomal enzymes (dipeptidyl aminopeptidase I, cathepsins L and D) showed significantly increased activities in these tissues (the reason for which remains to be determined). We conclude that the effect of pirimiphos-methyl on proteolytic enzyme activities differs in different target tissues, and that pirimiphos-methyl induced inhibition of proteases in liver tissue may represent a previously unrecognised toxicity hazard in higher animals.
authors.affiliation: Department of Neurochemistry, Newcastle General Hospital, Newcastle upon Tyne, UK.
authors.forename: D
authors.initials: D
authors.lastname: Mantle
authors.forename: M A
authors.initials: MA
authors.lastname: Saleem
authors.forename: F M
authors.initials: FM
authors.lastname: Williams
authors.forename: R M
authors.initials: RM
authors.lastname: Wilkins
authors.forename: A R
authors.initials: AR
authors.lastname: Shakoori
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D004789:Enzyme Activation / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010447:Peptide Hydrolases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007306:Insecticides; D009946:Organothiophosphorus Compounds; C014153:pirimiphos methyl; D010447:Peptide Hydrolases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases