Loss of striatal angiotensin-converting enzyme following intrastriatal AF64A is not related to destruction of cholinergic interneurons.
The potent angiotensin-converting enzyme (ACE) inhibitor 351A was radioiodinated (125I-351A) and used to quantitate ACE in the striatum of rats treated with the cholinergic neurotoxin AF64A. Unilateral administration of 4 nmol of AF64A into the striatum, which caused a 42% reduction in striatal choline acetyltransferase (ChAT) activity, reduced binding of 125I-351A in the lesioned striatum by 37% relative to the untreated striatum. The AF64A treatment also reduced the dopamine (DA) concentration by 59% in the lesioned striatum, but did not significantly reduce the serotonin (5-HT) concentration. Despite the reductions in ACE and these neurochemical markers, there was no significant correlation between the extent of reduction of the specific neurochemical markers and ACE. These results suggest that the AF64A treatment caused non-specific damage to striatal non-cholinergic neurons as well as destroying cholinergic neurons, and that ACE is contained in non-cholinergic neurons.
Walters
D E
DE
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164.
Speth
R C
RC
D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004151:Dipeptides / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects / Q000201:enzymology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001388:Aziridines; D004151:Dipeptides; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D007703:Peptidyl-Dipeptidase A; D002794:Choline