The effect of acute dyflos (DFP) treatment on [3H]nicotine binding to mouse brain homogenate

J Pharm Pharmacol. 1988 Nov;40(11):793-7. doi: 10.1111/j.2042-7158.1988.tb05174.x.

Abstract

One possible adaptive mechanism that might arise due to inhibition of cholinesterase in the brain is a down regulation of central cholinergic receptors. Therefore studies were performed to determine the effect of acute dyflos exposure on [3H]nicotine binding. Specific [3H] nicotine binding was demonstrated to be saturable, reversible, stereospecific, and inhibited by a number of nicotinic compounds. Scatchard analysis of specific [3H] nicotine binding produced a curvilinear plot that was resolved into high- and low-affinity sites with Kd values of 6.1 +/- 2.5 and 114 +/- 13 nM, and Bmax values of 11.8 +/- 3.5 and 182 +/- 24 fmol (mg protein)-1, respectively. The nicotinic binding sites in brain homogenate from dyflos-treated mice that were killed 20 min or 10 h after exposure did not exhibit significant alterations in binding parameters from control mouse brain homogenate. However, brain homogenate from treated mice that were killed 24 h after exposure resulted in statistically significant differences in the low-affinity K(D) and Bmax values from controls. Since no alterations were found in the high-affinity binding parameters and dyflos had only a minimal effect on the low-affinity site at 24 h, it was concluded that nicotinic receptor down regulation does not appear to be the mechanism through which the mouse functionally adapts to cholinesterase inhibition caused by acute dyflos treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Isoflurophate / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nicotine / metabolism*
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism

Substances

  • Receptors, Nicotinic
  • Isoflurophate
  • Nicotine