Functional changes of nicotinic acetylcholine receptor in muscle and lymphocyte of myasthenic rats following acute dimethoate poisoning.

Abstract

The mechanism underlying intermediate myasthenia syndrome (IMS) following acute organophosphate poisoning remains largely unknown. Previous studies indicated that the mechanism of myasthenia in rats and IMS patients is most likely due to a postsynaptic neurotransmission blocking at neuromuscular junctions (NMJ). Nicotinic acetylcholine receptor (nAChR) is a key postsynaptic component at NMJ. Whether functional changes of nAChR are related to the development of myasthenia has not been demonstrated and addressed in vivo so far. In this study, we attempted to investigate temporal and spatial changes of nAChR in the blood lymphocyte, muscle and brain of rats during the course of myasthenia after acute dimethoate poisoning by using radioligand-binding assay. We found that specific nAChR binding activity in the gastrocnemius muscle and blood lymphocytes of myasthenia rats was significantly increased at 48h after dimethoate poisoning. However, no changes of nAChR binding activity were found in the lymphocytes and muscle of non-myasthenia rats which were sacrificed at 1h after intoxication. Interestingly, no changes of nAChR and muscarinic acetylcholine receptor (mAChR) binding activity were found in the cerebrum and cerebellum of all rats after dimethoate intoxication either at 1 or 48h. The change of nAChR specific binding activity in the lymphocytes is parallel with that in the skeletal muscle during the development of myasthenia. This implied that the changes of nAChR receptor binding activity in the skeletal muscle and lymphocytes are highly associated with the development of myasthenia. The functional changes of nAChR at NMJ might play an important role in the paralysis of skeletal muscle following acute organophosphates (OPs) poisoning.

• Authors: Dongren Yang, Yong Niu, Fengsheng He
• Journal: Toxicology (Toxicology) Vol. 211 Issue 1-2 Pg. 149-55 (Jul 01 2005) ISSN: 0300-483X [Print] Ireland
• PMID: 15863258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insecticides
• Muscarinic Antagonists
• Receptors, Nicotinic
• Quinuclidinyl Benzilate
• Nicotine
• Dimethoate

Topics

• Animals
• Brain (metabolism)
• Dimethoate (toxicity)
• Insecticides (toxicity)
• Lymphocytes (metabolism)
• Male
• Muscarinic Antagonists (toxicity)
• Muscles (metabolism)
• Myasthenic Syndromes, Congenital (chemically induced, metabolism)
• Nicotine (metabolism)
• Quinuclidinyl Benzilate (toxicity)
• Radioligand Assay
• Rats
• Rats, Wistar
• Receptors, Nicotinic (metabolism)
• Tissue Distribution