The use of the rat iris as a model system to evaluate the effect of the cholinotoxin, AF64A, in vivo.
The iris is innervated by both cholinergic parasympathetic, and adrenergic sympathetic branches of the autonomic nervous system. This innervation represents a simple and anatomically well-defined system to evaluate the effects of chemical compounds on cholinergic and adrenergic neurons. AF64A (acetyl ethylcholine aziridinium) is a known cholinotoxin in the brain and, in these experiments using the iris system, we evaluated its in vivo effect on cholinergic enzyme activity, pupillary size, and catecholamine neurotransmitter levels. We found in this system that AF64A reduces the activity of choline acetyltransferase (ChAT) but not acetylcholinesterase (AChE). AF64A is selective for cholinergic neurons, since norepinephrine and dopamine levels were unaffected.
Willson
C A
CA
Loyola University Chicago Stritch School of Medicine, Department of Pharmacology, Maywood, IL 60153, USA.
Luthman
J
J
Hoffer
B
B
Hanin
I
I
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D007498:Iris / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D018377:Neurotransmitter Agents; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline