Tetrahydroaminoacridine but not 4-aminopyridine inhibits high-affinity choline uptake in striatal and hippocampal synaptosomes.
We have compared the effects of tetrahydroaminoacridine (THA), 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on high affinity choline uptake and the release of newly synthesized acetylcholine (ACh) from striatal and hippocampal synaptosomes, and on choline acetyltransferase (ChAT) activity in rat striatal synaptosomes. Incubation of the striatal synaptosomes with various THA concentrations (5-100 microM) caused a concentration-dependent inhibition in their accumulation of soluble 14C-labeled compounds ([14C]choline and [14C]ACh); at concentrations of 50 microM or greater the THA also completely suppressed the release of newly synthesized [14C]ACh. 4-AP slightly but significantly decreased the accumulation of the [14C]ACh in the striatal synaptosomes, without affecting that of [14C]choline, but markedly increased the release of [14C]ACh into the medium; hence the drug stimulated net choline uptake (by 19, 20 and 31%, respectively, in the presence of 5, 50 and 100 microM concentrations). Like THA, but not 4-AP, TEA decreased both the accumulation of soluble 14C-compounds in the striatal synaptosomes and the release of newly synthesized [14C]ACh. Similar effects of THA and 4-AP on HACU and the release of [14C]ACh were also observed when hippocampal synaptosomes were used. THA and 4-AP are structurally similar, and share with TEA the ability to block certain potassium channels. Present data show that, in spite of these similarities, these compounds produce opposite effects on net choline uptake by striatal and hippocampal synaptosomes.
Buyukuysal
R L
RL
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Wurtman
R J
RJ
D015761:4-Aminopyridine; D000609:Aminoacridines / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002794:Choline / Q000493:pharmacokinetics*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology*
D000609:Aminoacridines; D000631:Aminopyridines; D013619:Tacrine; D015761:4-Aminopyridine; D002795:Choline O-Acetyltransferase; D002794:Choline