Autoreceptor preference of dopamine D2 receptor agonist correlates with preferential coupling to cyclic AMP

Dopamine autoreceptors control the synaptic release and turnover of dopamine. Some dopamine agonists display a preference for modulation of autoreceptor functions rather than postsynaptic-driven behaviors. However, the nature of this apparent selectivity is still elusive. To investigate this property, we have used an heterologous expression system in which D-2S receptors are coupled to both inhibition of cyclic AMP levels and stimulation of inositol triphosphate production. We show that D-2-like receptor agonists display distinct potencies on these two second messenger pathways; Moreover, a strong correlation is observed between the potency of agonists to interact with adenylate cyclase and their potency to modulate autoreceptor functions. Such a correlation does not show up with the phospholipase C pathway. This suggests that autoreceptor preference of D-2-like receptor agonists may be driven by a preferential interaction with a second messenger system. NeuroReport 12:1473-1479 (C) 2001 Lippincott Williams & Wilkins.