title: Differential blocking actions of 4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) and gamma-hexachlorocyclohexane (gamma-HCH) on gamma-aminobutyric acid- and glutamate-induced responses of American cockroach neurons.
abstract: 4'-Ethynyl-4-n-propylbicycloorthobenzoate (EBOB) has been employed extensively as a radioligand in binding assays to evaluate the pharmacology of gamma-aminobutyric acid (GABA)-gated Cl- channels (GABARs) of insects and mammals, and gamma-hexachlorocyclohexane (gamma-HCH) was used as an insecticide targeting insect GABARs. Since recent studies have shown that not only GABARs but also glutamate-gated chloride channels (GluCls) are blocked by picrotoxinin, dieldrin and fipronil, the actions of EBOB and gamma-HCH on native GABARs and GluCls of terminal abdominal ganglion neurons in American cockroach (Periplaneta americana) were tested using patch-clamp electrophysiology. A marked run-down of the GABA- and glutamate-induced responses of the cockroach neurons occurred, when a standard pipette solution was employed, but addition of pyruvate to the solution permitted stable recordings of these responses. With this solution, EBOB and gamma-HCH were found to block not only the GABA- but also glutamate-gated responses, with the actions augmented by repeated co-application with the agonists. It was also found that prolonged pre-application of EBOB and gamma-HCH prior to co-application with GABA and glutamate resulted in enhanced blocking actions, indicating resting-state actions of the blockers. The blocking actions of EBOB and gamma-HCH on the GABA- and glutamate-induced responses were compared by determining IC50 values under steady state condition. The IC50 values for the actions of EBOB on GABAR and GluCls differed less than those of gamma-HCH.
authors.affiliation: Department of Applied Biological Chemistry, School of Agriculture, Kinki University, 3327-204, Nakamachi, Nara, 631-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okuda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ozoe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D018118:Chloride Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010526:Periplaneta; D018079:Receptors, GABA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D007306:Insecticides; D018079:Receptors, GABA; D017470:Receptors, Glutamate; C091518:1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001556:Hexachlorocyclohexane