Specific Receptor-Mediated Inhibition of Cyclic AMP Synthesis by Dopamine in a Neuroblastoma × Brain Hybrid Cell Line NCB-20

Abstract

Dopamine [DA] and DA receptor agonists inhibit adenylate cyclase activity dose-dependently in a neuroblastoma .times. Chinese hamster brain explant hybrid cell line NCB-20. Apomorphine (with an IC50 [50% inhibition concentration] value of 10 nM) was the most effective inhibitor, followed by 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthaline (ADTN), DA, and N-dipropyldopamine. The inhibition was potently reversed by sulpiride, butaclamol and flupenthixol in a stereospecific manner, but was unaffected by yohimbine, except at high concentrations. Clonidine also inhibited adenylate cyclase activity in these cells and this was reversed by the .alpha.2-adrenoceptor antagonist yohimbine, but not by sulpiride. [D-Ala2, D-Leu5]Enkephalin inhibited adenylate cyclase activity in NCB-20 cells at nM concentrations; this was reversed by naloxone. All 3 inhibitory neurotransmitters were able to reverse the stimulation of cAMP synthesis by serotonin [5-hydroxytryptamine] or prostaglandin E1. The DA receptor that modulates cAMP synthesis in NCB-20 cells is pharmacologically quite distinct from a high-affinity spiperone binding site identified in these cells, but shows the pharmacologic specificity of the D2 receptor previously described in mammalian brain.