IN-VIVO INHIBITION BY MIPAFOX OF SOLUBLE AND PARTICULATE FORMS OF ORGANOPHOSPHORUS NEUROPATHY TARGET ESTERASE (NTE) IN HEN SCIATIC-NERVE

Neuropathy target esterase (NTE) is a protein suggested to be involved in the initiation mechanism of organophosphorus-induced delayed neuro pathy (OPIDP). We previously described two different forms of NTE acti vity in hen sciatic nerve: a particulate form (P-NTE) representing 40- 50% of total NTE activity in sciatic nerve, and a remaining soluble co mponent (S-NTE). In brain tissue on the other hand, more than 90% of N TE activity was recovered as P-NTE. In this work we studied the in viv o inhibition of both NTE forms with different doses of mipafox and the results were compared with sensitivity to mipafox in vitro. The highe st dose with no observable neuropathic effects (1.5 mg/kg mipafox p.o. ) inhibited 33% P-NTE and 55% S-NTE activity. The difference between P -NTE and S-NTE activity was statistically significant (P < 0.001, n = 9). Higher doses (3 mg/kg) induced neuropathy and inhibited NTE more t han 75%, but differences between P- and S-NTE were not significant (P > 0.5). The greater inhibition of S-NTE than P-NTE in vivo contrasts w ith the observation that S-NTE is less sensitive in vitro.