Mechanism of aminopyridine-induced release of [3H]dopamine from rat brain synaptosomes.
1. Aminopyridines (APs) induced the release of [3H]dopamine (3H-DA) from rat synaptosomal preparations. 2. 4-AP and 3,4-DAP were of equal efficacy in inducing release of 3H-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 3H-DA (IC50 approximately 4 microM) than Co2+ and Ni2+ (IC50s approximately 500 microM). 4. While 4-AP increased the 45Ca2+ content of whole synaptosomal preparations, no effect of 4-AP on 45Ca2+ content was observed in lysed synaptosomal preparations. 5. 4-AP-induced 45Ca2+ uptake was inhibited by Cd2+, Ni2+ and Co2+ in concentration ranges similar to those inhibiting 3H-DA release.
Scheer
H W
HW
Department of Pharmacology, University of Montreal, Canada.
Lavoie
P A
PA
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D003035:Cobalt / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000631:Aminopyridines; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D018377:Neurotransmitter Agents; D002104:Cadmium; D003035:Cobalt; D015761:4-Aminopyridine; D000077770:Amifampridine; D002118:Calcium; D004298:Dopamine