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

Abstract: Dopamine and dopamine receptor agonists were found to inhibit adenylate cyclase activity dose-de-β ndently in a neuroblastoma × Chinese hamster brain explant hybrid cell line NCB-20. Apomorphine (with an IC₅₀ value of 10 n M ) was the most effective inhibitor, followed by 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydro-naphthaline (ADTN), dopamine, and N -dipropyldopa-mine. 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 α₂-adrenoreceptor antagonist yohimbine, but not by sulpiride. d -Ala², d -Leu⁵]Enkephalin inhibited adenylate cyclase activity in NCB-20 cells at nanomolar concentrations; this was reversed by naloxone. All three inhibitory neurotransmitters were able to reverse the stimulation of cyclic AMP synthesis by serotonin or prostaglandin E₁The dopamine receptor that modulates cyclic AMP 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.