D1-like dopaminergic activation of phosphoinositide hydrolysis is independent of D(1A) dopamine receptors: Evidence from D(1A) knockout mice

Eitan Friedman, Li Qing Jin, Guo Ping Cai, Tom R. Hollon, John Drago, David R. Sibley, Hoau Yan Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Accumulated evidence suggests that dopamine and dopamine D1 agonists 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 D(1A) 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 D(1A) site plays a role in stimulating phosphoinositide hydrolysis by using the dopamine D(1A)-deficient mutant mice as a test model. Results show that although D1 dopamine receptor-mediated production of cAMP is completely absent in membranes of D(1A)-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 G(αs) is markedly reduced, although coupling of [3H]SCH23390 binding sites to G(αq) was unaltered in tissue taken from D(1A) 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 D(1A) receptor that activates adenylyl cyclase.

Original languageEnglish
Pages (from-to)6-11
Number of pages6
JournalMolecular Pharmacology
Volume51
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

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