Cecal ligation and puncture peritonitis model shows decreased nicotinic acetylcholine receptor numbers in rat muscle: immunopathologic mechanisms?
BACKGROUND
Although systemic inflammation is believed to cause upregulation of nicotinic acetylcholine receptors (nAchRs) in muscle, chronic infections such as Chagas' disease occasionally are complicated by myasthenia gravis. The authors investigated how a nonlethal cecal ligation and puncture (CLP) peritonitis model in rats could affect muscle nAchR.


METHODS
On day 1, 4, 7, 14, or 21 after CLP or sham operation, nAchR binding was assayed in the anterior tibial muscle and diaphragm using [125I]alpha-bungarotoxin. The presence or absence of weakness, in vivo dose-response relationships for d-tubocurarine, and serum anti-nAchR antibody titers were assayed in separate experiments.


RESULTS
Systemic inflammation was most severe during the first 4 to 5 days. Numbers of nAchRs were decreased in anterior tibial muscle on days 7, 14, and 21 after CLP, and in the diaphragm on days 7 and 14 (P < 0.01). Both 50% and 90% blocking doses of d-tubocurarine) were lower in CLP rats than in sham-operated rats on days 7, 14, and 21 (P < .05). Weakness was overt in approximately half of CLP rats at these times. Serum anti-nAchR antibody (0.7-1.4 nM) was detectable beginning on day 4 and continuing throughout the 21-day observation period in 58-67% of CLP rats.


CONCLUSIONS
During the recovery phase of injury, nonlethal CLP peritonitis resulted in downregulation of nAchR. However, further study is needed to determine the role of anti-nAchR antibodies in the development of decreased receptor numbers and impaired neuromuscular function.
Tsukagoshi
H
H
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Gunma-Ken, Japan.
Morita
T
T
Takahashi
K
K
Kunimoto
F
F
Goto
F
F
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002432:Cecum; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005966:Glucuronidase / Q000097:blood; D008026:Ligation; D008297:Male; D009043:Motor Activity; D009132:Muscles / Q000737:chemistry*; D010538:Peritonitis / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000032:analysis* / Q000276:immunology; D014403:Tubocurarine / Q000494:pharmacology; D015430:Weight Gain
D001323:Autoantibodies; D011978:Receptors, Nicotinic; D000242:Cyclic AMP; D005966:Glucuronidase; D014403:Tubocurarine