Role of ion channels and intraterminal calcium homeostasis in the action of deltamethrin at presynaptic nerve terminals.
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.
Clark
J M
JM
Department of Entomology, University of Massachusetts, Amherst 01003.
Brooks
M W
MW
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D009570:Nitriles; D009638:Norepinephrine / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C060269:D 595; C017180:decamethrin; D013779:Tetrodotoxin; D014700:Verapamil; D002118:Calcium; D010433:Pentylenetetrazole; D009638:Norepinephrine