Functional Interactive Effects of D1 and D2 Dopamine Receptor Blockade
Multiple types of dopamine (DA) receptors have been shown to exist in the striatum (Seeman, 1980). These receptor populations have been divided into those which stimulate the enzyme adenylate cyclase (D2 sites) and those which are not directly linked to or suppress this enzyme (D2 sites, Kebabian and Calne, 1978; Stoof and Kebabian, 1984). Until now, the functional effects of DA receptor activation in the brain have been attributed to drug action at D2 receptor sites. Thus, good correlations exist between the ability of neuroleptic drugs to displace 3H-spiroperidol from specific binding sites on D2 receptors (Seeman, 1980) and their antipsychotic activity (Seeman, 1977; Creese et al., 1979; Seeman, 1980). Although no obvious physiological function for D1 sites in brain is known, recent evidence has suggested an interaction between D1 and D2 sites. For example, SKF 38393, a D1 agonist, stimulates the efflux of cAMP from superfused striatal tissue slices, and this stimulation is antagonized by LY 141865, a selective D2 agonist.
KeywordsAdenylate Cyclase Receptor Blockade
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