Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated efflux of cyclic AMP and K+-stimulated release of acetylcholine from rat neostriatum

Abstract

Two types of dopamine receptors whose stimulation affect cAMP efflux (and by inference formation) could be identified in rat neostriatum. One type of receptor, called D-1 receptor, increased cAMP efflux whereas stimulation of a second type of dopamine receptor, called D-2 receptor, was followed by a reduction in cAMP efflux induced by stimulation with a D-1 receptor agonist. D-2 receptor agonists inhibited the effects of D-1 receptor agonists on cAMP efflux in a non-competitive way. These inhibiting effects of D-2 receptor agonists occurred also in the absence of Ca2+-ions which could imply that some of the D-2 receptors are located on cells possessing D-1 receptors. The dopamine receptor mediating inhibition of the release of radiolabeled acetylcholine (ACh) in the neostriatum appeared to have the same pharmacological characteristics as the D-2 dopamine receptor mediating the inhibition of the D-1 receptor agonist induced cAMP efflux. Selective D-2 receptor agonists like LY 141865 and RU 24926 stimulated this receptor while the D-1 receptor agonist SKF 38393 was inactive. Effects of the selective D-2 receptor agonists could be antagonized by (-)-sulpiride, a selective D-2 receptor antagonist. Although the pharmacological characteristics of the dopamine receptors mediating inhibition of both ACh release and (D-1 dopamine receptor agonist induced) cAMP efflux appeared to be similar, drugs stimulating cAMP efflux did not affect ACh release or LY 141865 induced inhibition of ACh release from rat neostriatum. Therefore it is still questionable whether the dopamine receptor mediating inhibition of both ACh release and cAMP efflux is one and the same functional entity.