MECHANISM OF AMINOPYRIDINE-INDUCED RELEASE OF [H-3] DOPAMINE FROM RAT-BRAIN SYNAPTOSOMES

1. Aminopyridines (APs) induced the release of [H-3]dopamine (H-3-DA) from rat synaptosomal preparations. 2. 4-PA and 3,4-DAP were of equal efficacy in inducing release of H-3-DA; 3-AP, 2-AP and 2,6-AP were less active; pyridine and pyridine-4-carboxylamide were inactive. 3. Cd2+ was more effective in inhibiting 4-AP-induced release of H-3-DA (IC50 almost-equal-to 4-mu-M) than Co2+ and Ni2+ (IC50s almost-equal-to 500-mu-M). 4. While 4-AP increased the Ca-45(2+) content of whole synaptosomal preparations, no effect of 4-AP on Ca-45(2+) content was observed in lysed synaptosomal preparations. 5. 4-AP-induced Ca-45(2+) uptake was inhibited by Cd2+, Ni2+ and Co2+ in concentration ranges similar to those inhibiting H-3-DA release.