Interactions of tetramethrin, fenvalerate and DDT at the sodium channel in rat dorsal root ganglion neurons.
Type I and type II pyrethroids and dichlorodiphenyltrichloroethane (DDT) are known to modulate the sodium channel to cause the hyperexcitatory symptoms of poisoning in animals. However, since the degrees to which neuronal sodium channel parameters are altered differ, a question is raised as to whether these insecticides bind to the same site in the sodium channel. Competition patch-clamp experiments were performed using rat dorsal root ganglion neurons which are endowed with tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. D-trans-Tetramethrin, S,S-fenvalerate and p,p'-DDT caused a slowly rising and slowly falling tail current to be developed in tetrodotoxin-sensitive sodium channels. In tetrodotoxin-resistant sodium channels, these insecticides, particularly tetramethrin and fenvalerate, generated a large and prolonged tail current upon repolarization. The effects of tetramethrin were reversible after washing with drug-free solution, whereas the effects of fenvalerate and DDT were irreversible. When fenvalerate application was followed by tetramethrin application, the characteristic changes in current by fenvalerate disappeared and the characteristic changes by tetramethrin appeared. After washout, the characteristic current pattern of fenvalerate reappeared. These results can be explained by assuming that the tetramethrin molecule displaces the fenvalerate molecule from the same binding site in the sodium channel protein, or that tetramethrin and fenvalerate bind to separate sodium channel sites which interact allosterically with each other. DDT interacted with fenvalerate and tetramethrin in the same manner.
Song
J H
JH
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Nagata
K
K
Tatebayashi
H
H
Narahashi
T
T
D000818:Animals; D000831:Animals, Newborn; D003634:DDT / Q000494:pharmacology*; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects; D005727:Ganglia, Spinal / Q000502:physiology*; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D007536:Isomerism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles; D018408:Patch-Clamp Techniques; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; D013779:Tetrodotoxin; D003634:DDT; C017690:fenvalerate; C009424:tetramethrin