Modulation of the SNARE core complex by dopamine

Communication between nerve cells in the brain occurs primarily through spe cialized junctions called synapses. Recently, many details of synaptic tran smission have emerged. The identities of specific proteins important for sy naptic vesicle release have now been established. We have investigated thre e synaptic proteins, VAMP (vesicle associated membrane protein; also called synaptobrevin), syntaxin, and SNAP25 (synaptosomal associated protein of 2 5kDa) as possible targets in the dopamine-mediated modulation of synaptic f unction in rat striatal slices. These three proteins form a SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptors) core complex that is known to be essential for synaptic transmission. Although it is en visioned that the SNAREs undergo dynamic and cyclic interactions to elicit synaptic vesicle release, their precise functions in neurotransmission rema ins unknown. We have examined SNARE complexes in intact rat striatal slices . Cellular proteins were solubilized, separated electrophoretically by SDS- PAGE, and then identified immunologically. Application of dopamine to stria tal slices results in SNAREs favoring the SNARE core complex, a complex whi ch forms spontaneously in the absence of crosslinking agents, rather than t he monomer form. In addition, rapid crosslinking of dopamine-treated striat al slices demonstrates that the SNARE complex is increased 4 fold in dopami ne treated striatal slices compared with control slices. Haloperidol blocke d the dopamine-induced change in the core complex. These results suggest th at changes in the activities of SNAREs may be involved in the underlying ce llular mechanisms(s) of dopamine-regulated synaptic plasticity of the stria tum.