title: Differential long-term effect of AF64A on [3H]ACh synthesis and release in rat hippocampal synaptosomes.
abstract: The activities of various presynaptic cholinergic parameters were determined in hippocampal synaptosomes of rats 29 weeks after intracerebroventricular injection of ethylcholine aziridinium (AF64A) (3 nmol/2 microliters/side) or vehicle (saline). Synaptosomes were preloaded with [3H]choline ([3H]Ch), treated with diisopropyl fluorophosphate to inhibit cholinesterase activity and then were assayed for their content of [3H]Ch and [3H]acetylcholine ([3H]ACh) and for their ability to synthesize and release [3H]ACh. In synaptosomes from AF64A-treated rats compared with synaptosomes from vehicle-treated rats we observed that: (i) specific uptake of [3H]Ch was reduced to 60% of control; (ii) residing [3H]ACh levels were 43% of control while residing [3H]Ch levels were 72% of control; (iii) basal and K(+)-induced [3H]ACh release were 77% and 73% of control, respectively; (iv) high K(+)-induced synthesis of [3H]ACh was only 9% of control; (v) but, choline acetyltransferase activity remained relatively high, being 80% of control. These results suggest that AF64A-induced cholinergic hypofunction is expressed by both loss of some cholinergic neurons and impairment in the functioning of the spared neurons.
authors.affiliation: Department of Organic and Medicinal Chemistry, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Z
authors.initials: Z
authors.lastname: Pittel
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Fisher
authors.forename: E
authors.initials: E
authors.lastname: Heldman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology; D014316:Tritium
chemical_list: D001388:Aziridines; D014118:Toxins, Biological; D014316:Tritium; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine