Intracerebroventricular administration of ethylcholine mustard aziridinium ion (AF64A) reduces release of acetylcholine from rat hippocampal slices.
Ethylcholine mustard aziridinium ion (AF64A), or vehicle, was infused bilaterally (3 nmol/3 microliter per side) into the lateral ventricles of rats. The effect of such treatment on various cholinergic responses was measured in the hippocampus, cortex and striatum. Potassium-stimulated release of acetylcholine from superfused slices of hippocampus was reduced, 7 and 21 days after treatment with AF64A, to 24 and 35% of control, respectively. The activity of choline acetyltransferase in the hippocampus also decreased, to 42% of control, both 7 and 21 days after treatment with AF64A. Similarly, the activity of acetylcholinesterase and the high affinity transport of choline in the hippocampus were reduced, to 40 and 30% of control; and to 33 and 48% of control, respectively, 7 and 21 days after treatment with AF64A. Synthesis of acetylcholine in slices of hippocampus was also decreased after treatment with AF64A (71 and 51% of control, 7 and 21 days post-AF64A respectively). Only the binding of [3H]QNB in the hippocampus was unchanged at 7 days after treatment with AF64A, although a small reduction (11%) was noted 21 days after treatment with AF64A. The activity of choline acetyltransferase and acetylcholinesterase, the high-affinity transport of choline and the binding of [3H]QNB in cortex and striatum were unaffected by treatment with AF64A under the same experimental conditions. Using a substantially smaller dose than that earlier reported in mice, the earlier finding was thus confirmed, and extended, in rats, of a highly selective effect of AF64A on several components of the cholinergic system. Under the conditions of this study, these effects appeared to be confined to the hippocampus.
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats
D001388:Aziridines; D001389:Azirines; D011813:Quinuclidinyl Benzilate; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine