Chronic intraperitoneal endotoxin treatment in rats induces resistance to d-tubocurarine, but does not produce up-regulation of acetylcholine receptors.
BACKGROUND
Chronic systemic inflammation resulting from intraperitoneal Eschevichia coli endotoxin administration or Corynebacterium injections induces tolerance to non-depolarizing neuromuscular blockers in rodents. Although this has been explained as up-regulation of muscle acetylcholine receptors (AChR), the numbers of involved receptors have not been documented. The aim of this study was to determine the effects of chronic endotoxin administration on rat muscle AChR.


METHODS
One day after one, seven, or 14 daily intraperitoneal doses of lipopolysaccharide endotoxin (0 or 0.5 mg kg(-1)), we studied in vivo dose-response relationships for d-tubocurarine (d-Tc) and AChR binding using [125I]alpha-bungarotoxin as a ligand.


RESULTS
One day after seven and 14 daily intraperitoneal doses of endotoxin, the effective dose of d-Tc required to suppress the twitch response to 50% of the control (ED50) was significantly increased compared with that of time-matched control rats (146.5 +/- 38.2 vs. 76.1 +/- 9.0 microg kg(-1) for seven doses; 116.4 +/- 51.3 vs. 74.4 +/- 9.6 micro g kg-1 for 14 doses, P < 0.05). However, this was not associated with an increase in the number of AChR in the anterior tibial muscle or diaphragm.


CONCLUSIONS
Mechanisms other than AChR up-regulation might be responsible for the increased d-Tc requirement during chronic intraperitoneal endotoxin administration.
Hinohara
H
H
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine and Hospital, Maebashi, Japan. hinohara@showa.gunma-u.ac.jp
Morita
T
T
Okano
N
N
Kunimoto
F
F
Goto
F
F
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002038:Bungarotoxins / Q000494:pharmacology; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004731:Endotoxins / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D012132:Respiratory Muscles / Q000187:drug effects / Q000378:metabolism; D014403:Tubocurarine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
D002038:Bungarotoxins; D004731:Endotoxins; D008070:Lipopolysaccharides; D003473:Neuromuscular Nondepolarizing Agents; D011950:Receptors, Cholinergic; C044101:endotoxin, Escherichia coli; D005966:Glucuronidase; D014403:Tubocurarine