Soluble phenyl valerate esterases of hen sciatic nerve and the potentiation of organophosphate induced delayed polyneuropathy.
Contrary to some organophosphorus esters (OPs), certain esterase inhibitors including sulfonyl halides, carbamates and phosphinates do not cause axonal neuropathy, but they may exacerbate traumatic and some chemical insults to axons. This phenomenon is referred to as the promotion/potentiation of axonopathies. We report here promotion studies of the organophosphate induced delayed polyneuropathy (OPIDP). This neuropathy correlates with inhibition/aging of neuropathy target esterase, but this enzyme is not the target of promotion. Soluble phenyl valerate (PV) esterases in peak I (V(0)) of hen sciatic nerve were analysed. When these activities were inhibited in vitro by a mixture containing mipafox - an OP that causes OPIDP - paraoxon and p-toluene sulfonyl fluoride - two esterase inhibitors that do not cause either neuropathy or promotion-, then the remaining activity was sensitive to classical promoters such as phenylmethane sulfonyl fluoride (PMSF) and phenylmethyl benzyl carbamate. This PV-activity was not inhibited in sciatic nerves of hens treated with di-isopropyl phosphorofluoridate, at a dose that causes OPIDP. When these birds were further dosed with PMSF a dose-response relationship was observed between inhibition of PV-esterases, as above defined, and the severity of clinical responses. These data suggest that the target of promotion is embraced in peak I (V(0)) of soluble proteins of hen sciatic nerve.
Gambalunga
Alberto
A
Universita' degli Studi di Padova, Dipartimento di Medicina Ambientale e Sanita' Pubblica, Via Giustiniani 2, 30128 Padova, Italy.
Pasqualato
Fabiola
F
Lotti
Marcello
M
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D002645:Chickens; D002850:Chromatography, Gel; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D010755:Organophosphates / Q000633:toxicity*; D011115:Polyneuropathies / Q000139:chemically induced* / Q000201:enzymology*; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology*; D012995:Solubility; D013997:Time Factors
D004791:Enzyme Inhibitors; D010755:Organophosphates; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase