Enhancement of norepinephrine release from rat brain synaptosomes by alpha cyano pyrethroids

Abstract

Using a continuous perfusion system, synaptosomes prepared from rat brain readily took up l-[7,8- 3H]norepinephrine and released it in a calcium-dependent, potassium-stimulated manner. Of the insecticides tested, only pyrethroids which contained an alpha cyano grouping as part of their phenoxybenzyl alcohol moiety (i.e., deltamethrin, cypermethrin, and fenvalerate) enhanced calcium-dependent, potassium-stimulated release of [ 3H]norepinephrine. Non-cyano-pyrethroids (i.e., allethrin, des-cyano deltamethrin, des-cyano cypermethrin, and des-cyano fenvalerate) were greatly reduced in their ability to enhance [ 3H]norepinephrine release. None of the pyrethroids tested had any effect on [ 3H]norepinephrine uptake at concentrations at or below 10 −5 M. None of the pyrethroids tested at concentrations up to 10 −5 M had any effect on [ 3H]norepinephrine release from nondepolarized synaptosomes. The ED 50 dose of deltamethrin which resulted in half-maximal-enhanced [ 3H]norepinephrine release (i.e., 2.9 × 10 −9 M) correlated well with the ED 50 dose of deltamethrin which resulted in half-maximal-enhanced 45Ca uptake (i.e., 2.4 × 10 −9 M). Parathion and the noninsecticidal DDT analog, DDE, had no effect on [ 3H]norepinephrine uptake or release. DDT was found to be the most potent inhibitor of [ 3H]norepinephrine uptake.