Dopamine D 2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices

Abstract

Previous studies on the transduction mechanisms triggered by dopamine receptor stimulation have established that both D 1 and D 2 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 D 2 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 D 2 receptor. The rank order of potency was quinpirole (IC 50 5 nM) > lisuride (IC 50 8 nM) > RU 24213 (IC 50 50 nM) > dopamine (IC 50 200 nM). In contrast, selective D 1 receptor stimulation by fenoldopam did not alter the inositol monophosphate, inositol bisphosphate and inositol trisphosphate content. The quinpirole effect was prevented by selective D 2 antagonists, such as domperidone and l-sulpiride (both 5 μM) while it was unaffected by the selective D 1 antagonist SCH 23390 (100 nM) and by the pharmacologically inactive d-isomer of sulpiride. Our data indicate that the activation of striatal D 2 receptors leads to the inhibition of inositol phosphate production.