Recovery of activity and molecular forms of cholinesterase in different animal species following irreversible cholinesterase inhibition

Abstract

1. Diisopropoxyphosphorylfluoride and soman caused rapid decline of the cholinesterase (ChE) activity levels in earthworm, chicken, guinea pig, mouse and rat tissues. 2. The onset of recovery of ChE activity was well established within 5 days in all species except for the earthworm whose whole body ChE activity level remained low for at least 15 days. 3. Plasma ChE of the rat recovered to the normal activity level already in 6 days. After that, however, the activity level still continued to increase. This overshoot effect was much more pronounced in females than in males. 4. In females the activity level reached 50% above normal values after about 7 days. The overshoot of plasma ChE in the female rat still persisted 15 days after inhibition. 5. The overshoot of ChE activity was also observed in mouse and rat liver after inhibition. In the chicken ChE overshoot was not found. 6. The recovery of erythrocyte and brain ChE activity of the rat was observed to be slower than that of plasma and liver. Likewise the recovery of brain ChE activity of the mouse seemed to be slower than that of liver. Similar results were obtained for the chicken. Generally soluble ChE seem to recover faster than membrane bound. 7. In the case of erythrocyte and brain ChE the results indicated a similar ChE turnover as generally observed for other proteins in brain tissue. 8. In brain and retina of chicken as well as in rat brain and in guinea pig iris two distinct forms of ChE were found with marked different molecular weights. 9. In the chicken the activity of the form with a low molecular weight was found to predominate during the early recovery stages following ChE inhibition. At later stages the activity of a heavy weight form dominated. 10. In rat brain and retina as well as in guinea pig iris the activity of the form with the higher molecular weight was always predominating. 11. The results may, however, be interpreted such that the synthesis of the form of ChE with the lower molecular weight proceeds the appearance of the higher molecular weight form. 12. Administration of l-anserine nitrate, l-homocarnosine sulphate, l-carnosine and thyrotropin releasing hormone to the rats as well as primobolan to the mouse did not affect the recovery of activity and molecular forms of ChE following irreversible ChE inhibition. In the rats hypophysectomy was not found to affect the recovery either.