Jaw-Jou Kang (1), Yu-Wen Cheng and Wen-Mei Fu (2)
(1) Institute of Toxicology and (2) Department of Pharmacology, College
of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Section 1, Taipei,
Taiwan
Abstract: The effects of boldine [(S)2,9-dihydroxyl-1,10-dimethoxy-aporphine],
a major alkaloid in the leaves and bark of Boldo (Peumus boldus Mol.), on
neuromuscular transmission were studied using a muscle phrenic-nerve diaphragm
preparation. Boldine at concentrations lower than 200 microM preferentially
inhibited, after an initial period of twitch augmentation, the nerve-evoked
twitches of the mouse diaphragm and left the muscle-evoked twitches unaffected.
The twitch inhibition could be restored by neostigmine or washout with Krebs
solution. The twitches evoked indirectly and directly were both augmented
initially, suggesting that the twitch augmentation induced by boldine was
myogenic. Boldine inhibited the acetylcholine-induced contraction of denervated
diaphragm dose-dependently with an IC50 value of 13.5 microM.
At 50 microM, boldine specifically inhibited the amplitude of the miniature
end plate potential. In addition, boldine was similar to d-tubocurarine
in its action to reverse the neuromuscular blocking action of alpha-bungarotoxin.
These results showed that the neuromuscular blockade by boldine on isolated
mouse phrenic-nerve diaphragm might be due to its direct interaction with
the postsynaptic nicotinic acetylcholine receptor.
Keywords: Boldine, Peumus boldus Mol., Neuromuscular blockade, Acetylcholine
channel