AbstractIt has been almost 25 years since the classic studies first described the pyrethroid mode of action on voltage—dependent sodium channels. In the interval that followed, this electrophysiological approach has been enlarged upon using a variety of preparations with essentially the same result. Thus, there is little disagreement that pyrethroids have an action at or near the sodium channel in the nerve. Recently, a number of additional mechanisms have been suggested, including the perturbation of the voltage—dependent calcium channels. Using a functional bioassay that consists of a calcium—dependent, potassium—stimulated pulsed release of norepinephrine from rat brain synaptosomes, Type II pyrethroids caused a substantial enhancement of norepinephrine release that was not apparent when Type I pyrethroids were used. The ED50 dose of deltamethrin that resulted in half—maximal enhanced norepinephrine release (i.e., 2.9 × 10−9M) correlated well with the ED50 dose of deltamethrin that resulted in half—maximal enhanced45Ca uptake (i.e., 2.4 × 10−9M). Norepinephrine release was only partially blocked by tetrodotoxin and a calcium channel antagonist, D595. Deltamethrin enhanced norepinephrine release in the presence of tetrodotoxin but was unable to enhance release in the presence of D595. These results are supportive of a highly sensitive action of Type II pyrethroids at presynaptic nerve terminals in the central nervous system and of the involvement of voltage—depende
展开▼
