title: Cyclothiazide differentially modulates human metabotropic glutamate receptors linked to phosphoinositide hydrolysis stimulation in oocytes.
abstract: Cloned human metabotropic glutamate receptors, mGlu1 alpha and mGlu5 alpha, were functionally expressed in Xenopus oocytes. Cyclothiazide dose-dependently inhibited glutamate-stimulated human mGlu1 alpha responses (IC50 = 18 microM) in a non-competitive manner. In contrast, cyclothiazide slightly potentiated glutamate-stimulated human mGlu5 alpha responses. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8- methyl-endioxyl-5H-2,3-benzodiazepinehydrochloride) did not alter glutamate-stimulated human mGlu1 alpha or human mGlu5 alpha responses, either in the presence or absence of cyclothiazide. Thus, human metabotropic glutamate receptors coupled to phosphoinositide stimulation appear to contain sites sensitive to cyclothiazide but insensitive to GYKI 52466.
authors.affiliation: Lilly Research Laboratories 0424, Eli Lily and Co., Lilly Corporate Center Indianapolis, IN 46285.
authors.forename: R L
authors.initials: RL
authors.lastname: Sharp
authors.forename: N G
authors.initials: NG
authors.lastname: Mayne
authors.forename: J P
authors.initials: JP
authors.lastname: Burnett
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D001581:Benzothiadiazines / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D009865:Oocytes; D010716:Phosphatidylinositols / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D049993:Sodium Chloride Symporter Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D014151:Anti-Anxiety Agents; D001581:Benzothiadiazines; D004232:Diuretics; D018691:Excitatory Amino Acid Antagonists; D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; D049993:Sodium Chloride Symporter Inhibitors; C061950:GYKI 52466; D001569:Benzodiazepines; C004639:cyclothiazide