Muscarinic receptor dysfunction induced by exposure to low levels of soman vapor.
In the eye, it has been previously reported that exposure to a cholinesterase inhibitor results in a reduced miotic response following prolonged exposure and a decreased miotic response to the cholinergic agonists. However, no studies exist that characterize the effect of a single low-level vapor exposure to a nerve agent on parasympathetic function in the eye or determine the threshold dose for such an effect. The present study investigated the hypotheses that a single low-level exposure to soman vapor would result in dysfunction of the parasympathetic pathway mediating the pupillary light reflex resulting from a loss of muscarinic receptor function on the pupillary sphincter muscle. Adult male rats were exposed to soman vapor in a whole-body dynamic airflow exposure chamber. Rats exposed to low levels of soman vapor dose-dependently developed miosis (threshold dose between 4.1 and 6.1 mg-min/m3). Pupil size returned to preexposure levels within 48 h due to desensitization of pupillary muscarinic receptors, as assessed by the pupillary response to the muscarinic agonist oxotremorine. An attenuated pupillary light reflex was also present in miotic animals (threshold dose near 6.1 mg-min/m3). While pupil size recovers within 48 h, other measures of pupillary function, including the light reflex, acetylcholinesterase activity, and muscarinic receptor responsiveness, did not return to normal for up to 10 days postexposure. Recovery of the light reflex coincided with the recovery of pupillary muscarinic receptor function, suggesting that the attenuation of the light reflex was due to receptor desensitization.
Dabisch
Paul A
PA
Operational Toxicology Team, U.S. Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Maryland 21010-5424, USA. paul.a.dabisch@us.army.mil
Horsmon
Michael S
MS
Muse
William T
WT
Mioduszewski
Robert J
RJ
Thomson
Sandra
S
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation; D008297:Male; D015877:Miosis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012025:Reflex, Pupillary / Q000187:drug effects*; D012999:Soman / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D014835:Volatilization
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D012999:Soman; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase