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Spontaneous Reactivation of Planarian Acetylcholinesterase after Inhibition by Organophosphorate Pesticides, Diazinon and Chlorpyrifos
Author(s) -
Hirokawa Hideto,
Collins EvaMaria,
Hagstrom Danielle,
Radic Zoran,
Zhang Limin,
Taylor Palmer
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1191.6
Subject(s) - acetylcholinesterase , chemistry , butyrylcholinesterase , cholinergic , cholinesterase , diazinon , carboxylesterase , edrophonium , sarin , planarian , acetylcholine , aché , pharmacology , biochemistry , pesticide , enzyme , neostigmine , endocrinology , biology , microbiology and biotechnology , ecology , regeneration (biology)
Owing to its capacity to regenerate after amputation and a dominant cholinergic influence in motor activity, we have been studying the response of the freshwater planarian, Dugesia japonica , to cholinergic inhibitors such as organophosphate pesticides. In examining cholinesterase (ChE) and other carboxylesterase activities, we find that ~85% is acetylcholinesterase (AChE) activity, with slightly different specificities to the classic reversible inhibitors, such as edrophonium and BW286c51. Of particular interest in this planarian system is the capacity of diethylphosphoryl conjugates formed from Diazinon or other pesticide exposure to reactivate spontaneously, in vitro . A similar behavior has been noted in swine butyrylcholinesterase (BChE) as noted by Brazzolotto and colleagues (Abstracts XII Int. Cholinesterase Meeting), who have suggested that an altered tertiary structure in swine BChE may predispose ChE conjugates to spontaneous reactivation. Our studies show that spontaneous reactivation in planarians can be inhibited by classical cholinesterase inhibitors and by oximes that show limited nucleophilic activity, but can be enhanced by other oximes, particularly the zwitterionic oxime, RS194B. Further, spontaneous reactivation is enhanced at low pH, in contrast to the general base catalysis by oximes on small molecule alkylphosphorate esters and methylphosphonate esters. The observed reactivation kinetics suggest unique kinetic behaviors of H 2 O and various nucleophiles in the active center gorge of planarian AChE, perhaps dictated by hydrogen bonding and transient electric field influences in the AChE active center gorge. Support or Funding Information Supported by USPHS grant GM 18360 and NS 058046.