title: Pharmacological characterization of histamine-gated chloride channels from the housefly Musca domestica.
abstract: The biogenic amine histamine (HA) is not only the neurotransmitter of photoreceptors but also has important roles in mechanosensory reception, temperature preference, sleep and olfactory processing in insects. Two cDNAs (MdhclA and MdhclB) that encode HA-gated chloride channel subunits (MdHCLA and MdHCLB) were cloned from the housefly Musca domestica. The cRNAs were injected into Xenopus laevis oocytes to examine the functions and pharmacological characteristics of MdHCLA and MdHCLB channels using a two-electrode voltage clamp method. HA was used to activate MdHCLA and MdHCLB channels to evoke inward currents with EC50s of 33.1μM and 6.28μM, respectively. 2-(3-Trifluoromethylphenyl)histamine, an HA H1receptor agonist, was a partial agonist of MdHCLB receptors with an EC50of 49.4μM. MdHCLB channels were also activated by γ-aminobutyric acid (GABA) and monoamines, such as octopamine, serotonin (5-HT) and dopamine (DA); 5-HT and DA also acted as competitive antagonists. GABA acted as a full agonist of MdHCLB receptors with an EC50of 1.11mM. d-Tubocurarine, cimetidine and picrotoxinin were poor inhibitors of HA- and GABA-evoked currents in MdHCLB channels. Our data show that HCLB channels are more sensitive to agonists when compared with HCLA channels. HCLB channels are also affected by antagonists but insusceptible to known insecticides that target GABA- and glutamate-gated chloride channels.
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Kita
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Irie
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Ozoe
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan. Electronic address: ozoe-y@life.shimane-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ozoe
mesh_terms: D000818:Animals; D065101:Chloride Channel Agonists / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006793:Houseflies; D007306:Insecticides / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D009655:Octopamine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D065101:Chloride Channel Agonists; D018118:Chloride Channels; D018076:DNA, Complementary; D007306:Insecticides; D009655:Octopamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D004298:Dopamine
keywords: Agonists; Antagonists; Histamine; Histamine-gated chloride channel; Housefly