Dopamine D2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices

Previous studies on the transduction mechanisms triggered by dopamine receptor stimulation have established that both D₁ and D₂ subtypes of dopamine receptors are linked to the adenylate cyclase system, the former in a stimulatory and the latter in an inhibitory manner. The present report provides the first evidence that stimulation of D₂ receptors in rat brain tissue affects the turnover of polyphosphoinositides, a as revealed by changes of the content of inositol phosphates. We found that the basal level of [³H]inositol trisphosphate, [³H]inositol bisphosphate and [³H]inositol monophosphate decreased following the stimulation of the D₂ receptor. The rank order of potency was quinpirole (IC₅₀ 5 nM) > lisuride (IC₅₀ 8 nM) > RU 24213 (IC₅₀ 50 nM) > dopamine (IC₅₀ 200 nM). In contrast, selective D₁ receptor stimulation by fenoldopam did not alter the inositol monophosphate, inositol bisphosphate and inositol trisphosphate content. The quinpirole effect was prevented by selective D₂ antagonists, such as domperidone and l-sulpiride (both 5 μM) while it was unaffected by the selective D₁ antagonist SCH 23390 (100 nM) and by the pharmacologically inactive d-isomer of sulpiride. Our data indicate that the activation of striatal D₂ receptors leads to the inhibition of inositol phosphate production.