Studies on the neuromuscular blocking action of commercial paraquat in mouse phrenic nerve-diaphragm.
The neuromuscular blocking actions of commercial and pure paraquat on the mouse phrenic nerve-diaphragm were compared. Twitch responses of mouse diaphragm to nerve stimulation were inhibited by commercial paraquat (5-500 microM), but not by pure paraquat (1 mM). At concentrations greater than 30 microM, commercial paraquat also directly inhibited the contractions induced by electrical stimulation of the muscle. The inhibitory actions of commercial paraquat on twitches were potentiated by pretreatment with either 0.7 microM d-tubocurarine or 2.2 microM succinylcholine. Moreover, commercial paraquat inhibited acetylcholine contracture of the denervated mouse diaphragm. Similar to d-tubocurarine, commercial paraquat protected the diaphragms from inhibition by alpha-bungarotoxin and also inhibit the binding [125I]-alpha-bungarotoxin. Electrophysiological studies revealed that commercial paraquat inhibited the amplitude of miniature end-plate potentials (m.e.p.ps) and end-plate potentials (e.p.ps) of mouse diaphragm. The inhibition induced by commercial paraquat was frequency-dependent. All of these findings indicate that commercial paraquat possesses curare-like actions and inhibits muscle contractions by binding to the postsynaptic nicotinic acetylcholine receptors. Pure paraquat does not have these effects. Analysis of the components in commercial paraquat suggested that paraquat by-products and the added emulsifying agent were responsible for these observations. The clinical significance of these findings is that this neuromuscular blocking may contribute to the respiratory failure in paraquat intoxicated patients.
Lin-Shiau
S Y
SY
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Hsu
K S
KS
D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D004639:Emetics / Q000494:pharmacology; D005079:Excipients / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009045:Motor Endplate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000633:toxicity*; D018733:Nicotinic Antagonists; D010269:Paraquat / Q000633:toxicity*; D010791:Phrenic Nerve / Q000187:drug effects*; D011869:Radioligand Assay
D004639:Emetics; D005079:Excipients; D009466:Neuromuscular Blocking Agents; D018733:Nicotinic Antagonists; D010269:Paraquat