RT Journal Article
SR Electronic
T1 Dual action of the cyclodiene insecticide dieldrin on the gamma-aminobutyric acid receptor-chloride channel complex of rat dorsal root ganglion neurons.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 164
OP 171
VO 269
IS 1
A1 Nagata, K
A1 Narahashi, T
YR 1994
UL http://jpet.aspetjournals.org/content/269/1/164.abstract
AB The gamma-aminobutyric acidA (GABAA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide, and lindane. In order to elucidate the mechanisms of dieldrin interaction with the GABA system, whole-cell patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. When co-applied with GABA, dieldrin exerted a dual effect on the GABA-induced chloride current. The chloride current induced by 10 microM GABA was greatly enhanced by the first 20-sec co-application with 1 microM dieldrin, but the enhancement subsided during repeated co-applications, and the current was eventually suppressed below the control level. No recovery occurred after a prolonged washing with dieldrin-free solution. Desensitization of the chloride current was accelerated by dieldrin. However, when the period of co-application was limited to 2 sec, which was short enought to avoid desensitization, no suppression of current was observed during repeated co-applications and recovery occurred after washing. The desensitization and suppression occurred with an EC50 of 92 nM, whereas the enhancement required a higher EC50 at 754 nM. The GABA-induced chloride current comprised two components, one with a high sensitivity to dieldrin suppression with an EC50 of 5 nM and the other with a lower sensitivity with an EC50 of 92 nM. Dieldrin exerted its inhibitory effect on the GABA-induced current regardless of the presence or absence of pentobarbital and chlordiazepoxide. However, its effect was attenuated by the presence of picrotoxin. Furthermore, dieldrin suppressed the GABA-induced chloride current in a noncompetitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)