Abstract |
1. The curare-like action of 2,2',2''-tripyridine (a synthetic by-product of the herbicide, paraquat) was studied in mouse phrenic nerve-diaphragm preparation. The inhibition by 2,2',2''-tripyridine of nerve-evoked twitches was dependent on the concentration, ranging from 1 to 100 microM, which had no significant effect on the twitch amplitudes evoked by direct muscle stimulation. 2. The twitch inhibition by 2,2',2''-tripyridine was reversible and could be antagonized by anticholinesterase agents such as neostigmine, physostigmine as well as ecothiophate. 3. Pretreatment with either 0.7 microM (+)- tubocurarine or 2.2 microM succinylcholine shifted the concentration-inhibition curve of 2,2',2''-tripyridine to the left. 4. 2,2'2''-Tripyridine inhibited not only acetylcholine-induced contracture of the denervated mouse diaphragm but also that of the chick biventer cervicis muscle. Like (+)- tubocurarine, 2,2',2''-tripyridine protected the twitches from the inhibition by alpha-bungarotoxin and also specifically inhibited the binding of [125I]- alpha-bungarotoxin to the mouse diaphragm. All of these findings indicate that 2,2',2''-tripyridine possesses curare-like action and inhibits the muscle contractions through binding to postsynaptic acetylcholine receptors. 5. The postsynaptic inhibition exhibited by 2,2',2''-tripyridine was also implicated in the tetanic fade, a decrease in the amplitude of miniature endplate potential (m.e.p.p.) and endplate potential (e.p.p.). 6. The clinical implication of these findings is that 2,2',2''-tripyridine may be involved in the cause of respiratory failure in paraquat-intoxicated workers since 2,2',2''-tripyridine is a by-product of paraquat synthesis.
|
Authors | S Y Lin-Shiau, K S Hsu, W M Fu |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 106
Issue 1
Pg. 55-60
(May 1992)
ISSN: 0007-1188 [Print] England |
PMID | 1504731
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Bungarotoxins
- Cholinesterase Inhibitors
- Pyridines
- Receptors, Nicotinic
- 2,2',2''-terpyridine
- Succinylcholine
- Tubocurarine
|
Topics |
- Animals
- Bungarotoxins
(pharmacology)
- Chickens
- Cholinesterase Inhibitors
(pharmacology)
- Diaphragm
(drug effects)
- Drug Interactions
- Membrane Potentials
(drug effects)
- Mice
- Motor Endplate
(drug effects, physiology)
- Muscle Contraction
(drug effects)
- Neuromuscular Junction
(drug effects, physiology)
- Phrenic Nerve
(drug effects)
- Pyridines
(pharmacology)
- Receptors, Nicotinic
(drug effects, metabolism)
- Succinylcholine
(pharmacology)
- Tubocurarine
(pharmacology)
|