Cyclothiazide differentially modulates human metabotropic glutamate receptors linked to phosphoinositide hydrolysis stimulation in oocytes

Abstract

Cloned human metabotropic glutamate receptors, mGlu 1μ and mGlu 5μ, were functionally expressed in Xenopus oocytes. Cyclothiazide dose-dependently inhibited glutamate-stimulated human mGlu 1α responses (IC 50 = 18 μM) in a non-competitive manner. In contrast, cyclothiazide slightly potentiated glutamate-stimulated human mGlu 5α responses. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-endioxyl-5H-2,3-benzodiazepinehydrochloride) did not alter glutamate-stimulated human mGlu 1α or human mGlu 5α 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.