D-2-LIKE DOPAMINE AUTORECEPTOR ACTIVATION REDUCES QUANTAL SIZE IN PC12 CELLS

D-2-like dopamine autoreceptors regulate dopamine release and are impl icated in important actions of antipsychotic drugs and rewarding behav iors. To directly observe the effects of D-2 autoreceptors on exocytic neurotransmitter release, we measured quantal release of dopamine fro m pheochromocytoma PC12 cells that express D-2 and D-4 autoreceptors. High potassium-evoked secretion in PC12 cells produced a unimodal popu lation of quantal sizes. We found that exposures to the D-2-like agoni st quinpirole that inhibited tyrosine hydroxylase activity by similar to 50% also reduced quantal size by similar to 50%. The reduced quanta l size was blocked by the D-2 antagonist sulpiride and reversed by L-D OPA. Quinpirole also decreased the frequency of stimulation-evoked qua ntal release. Together, these findings indicate effects on quantal neu rotransmission by D-2-like dopamine autoreceptors previously distingui shed as synthesis-modulating autoreceptors that regulate tyrosine hydr oxylase activity Versus impulse-regulating autoreceptors that modulate membrane potential. The results also provide an initial demonstration of a receptor-mediated mechanism that alters quantal size.