[Potential biochemical mechanisms of neuromuscular junction transmission dysfunction induced by organophosphorus insecticides].
OBJECTIVE
To explore the potential biochemical mechanisms of neuromuscular junction transmission (NMJT) dysfunction induced by organophosphorus insecticides.


METHODS
Ten rats were dosed with phoxim (1,144 mg/kg) and 5 of them developed myasthenia. The NMJT function was evaluated by the mean consecutive differences (MCD) measured by stimulation single fiber electromyography (SSFEMG) with the frequency of stimuli at 20 Hz. The activity of Ca(2+)-ATPase, Na(+), K(+)-ATPase, cAMP dependent protein kinase (PKA), Ca(2+)/phospholipid dependent protein kinase (PKC), and tyrosine protein kinase (TPK) were determined.


RESULTS
In comparison with the control and non-myasthenic rats, the results in myasthenic rats showed that: (1) the MCDs increased; (2) the activities of Ca(2+)-ATPase, Na(+), K(+)-ATPase and PKA decreased and were negatively correlated with MCD; (3) the activities of PKC and TPK increased, and were positively correlated with MCD; (4) the phosphorylation of serine residuals in sarcolemma was weaker and the phosphorylation of tyrosine residuals was stronger.


CONCLUSIONS
The NMJT dysfunction is likely associated with the decrease in Ca(2+)-ATPase and Na(+), K(+)-ATPase activity. The acceleration of desensitization and prolongation of resensitization of nicotinic acetylcholine receptors occur following the increase in tyrosine phosphorylation and the decrease in serine phosphorylation induced by OPs poisoning.
Xiao
Cheng
C
National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
He
Feng-sheng
FS
Li
Qiu-sheng
QS
Niu
Yong
Y
Yu
Tao
T
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D004576:Electromyography / Q000187:drug effects; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D009157:Myasthenia Gravis / Q000139:chemically induced* / Q000201:enzymology; D009946:Organothiophosphorus Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats
D007306:Insecticides; D009946:Organothiophosphorus Compounds; C003135:phoxim; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases