PT - JOURNAL ARTICLE AU - Eitan Friedman AU - Li-Qing Jin AU - Guo-Ping Cai AU - Tom R. Hollon AU - John Drago AU - David R. Sibley AU - Hoau-Yan Wang TI - D<sub>1</sub>-like Dopaminergic Activation of Phosphoinositide Hydrolysis Is Independent of D<sub>1A</sub> Dopamine Receptors: Evidence from D<sub>1A</sub> Knockout Mice AID - 10.1124/mol.51.1.6 DP - 1997 Jan 01 TA - Molecular Pharmacology PG - 6--11 VI - 51 IP - 1 4099 - http://molpharm.aspetjournals.org/content/51/1/6.short 4100 - http://molpharm.aspetjournals.org/content/51/1/6.full SO - Mol Pharmacol1997 Jan 01; 51 AB - Accumulated evidence suggests that dopamine and dopamine D1agonists can activate phospholipase C in both brain and peripheral tissue. The receptor that mediates the hydrolysis of phosphoinositides has not been identified. The cloned dopamine D1A receptor that is generally thought to be linked to adenylyl cyclase, has also been proposed to couple to phospholipase C. However, a number of studies have suggested that this signaling pathway is mediated via a distinct D1-like dopamine receptor. We tested whether the D1A site plays a role in stimulating phosphoinositide hydrolysis by using the dopamine D1A-deficient mutant mice as a test model. Results show that although D1 dopamine receptor-mediated production of cAMP is completely absent in membranes of D1A-deficient mice, D1 receptor-mediated accumulation of inositol phosphate is identical in tissues of mutant and wild-type animals. Furthermore, the coupling of [3H]SCH23390 binding sites in striatal or frontal cortex membranes to Gαs is markedly reduced, although coupling of [3H]SCH23390 binding sites to Gαq was unaltered in tissue taken from D1A mutant mice compared with control animals. These results clearly demonstrate that dopaminergic stimulation of inositol phosphate formation is mediated by a D1 dopamine receptor subtype that is distinct from the D1A receptor that activates adenylyl cyclase.