Stimulation of synaptosomal dopamine synthesis by corticotropin-releasing factor in rat striatum: role of Ca 2+-dependent mechanisms

Abstract

Corticotropin-releasing factor (CRF) stimulated synaptosomal dopamine (DA) synthesis in rat striatal homogenates. The stimulatory effect of CRF was antagonized by α-helical CRF 9–41 and was dependent on the extracellular Ca 2+ concentration, being absent after removal of Ca 2+ from the incubation medium and maximal at about 1.2 mM extracellular Ca 2+. The stimulation of DA synthesis by forskolin (FSK) was less sensitive to a change of extracellular Ca 2+ concentration. 3-Isobutyl-1-methylxanthine potentiated the FSK effect but did not affect the response to CRF. CRF stimulation was additive to that produced by 40 mM KCl and was little affected by the calmodulin inhibitor, W-7, which markedly suppressed the veratridine-induced stimulation of DA synthesis. Polymyxin B antagonized the CRF stimulation while it had a weaker effect on FSK-stimulated DA synthesis. Tolbutamide reduced the FSK stimulation more effectively than the CRF response. CRF elicited a non-significant increase of cyclic AMP formation by striatal membranes. These results indicate that CRF stimulates striatal DA synthesis by a Ca 2+ -dependent mechanism possibly involving the activation of the protein kinase C pathway.