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Clark JM, Brooks MW: Role of ion channels and intraterminal calcium homeostasis in the action of deltamethrin at presynaptic nerve terminals. Biochem Pharmacol. 1989 Jul 15;38(14):2233-45.
Using a continuous perfusion system, synaptosomes prepared from rat brain released [3H] norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10 (-7) M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10 (-5) M), a phenethylamine-type calcium channel blocker, inhibited 21%. In combination, these two specific ion channel antagonists appear to function independently of each other in an additive fashion. Addition of deltamethrin to this preparation resulted in an enhanced release of [3H] norepinephrine which occurred in a biphasic fashion. At 10 (-7) M, deltamethrin produced a 42% enhancement in the first or initial peak of [3H] norepinephrine release and a 100% enhancement in the second or tailing peak. Addition of deltamethrin to tetrodotoxin-pretreated synaptosomes resulted in a net 37% enhancement of the initial peak release and a net increase of 277% in the tailing peak. Addition of deltamethrin to D595-pretreated synaptosomes produced no significant effect on enhanced [3H] norepinephrine release from either peak. Since tetrodotoxin is a specific sodium channel blocker, deltamethrin may be enhancing [3H] norepinephrine release by increasing the uptake of Ca2 via other voltage-gated channels (e.g. calcium) or exchange mechanisms in addition to its action at voltage-gated sodium channels. To determine whether deltamethrin may also have an effect on intraterminal Ca2+ homeostasis, external Ca2+ was replaced with Ba2+ and synaptosomes were depolarized with pentylenetetrazole (PTZ). At 10 (-5) M, deltamethrin produced a 66% increase in neurotransmitter release over that produced by PTZ alone. An estimated EC50 value of deltamethrin for PTZ-induced release was calculated to be 2.4 x 10 (-10) M. |
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