Inhibitory effects of alendronate on cholinergic responses in rat lower esophageal sphincter

Alendronate is a potent inhibitor of osteoclast-mediated bone resorption, but its use results in serious esophageal damage. In order to clarify the latter, we examined the effects of alendronate on electrical field stimulation-induced responses in the rat lower esophageal sphincter. Electrical field...

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Bibliographic Details
Published in:European journal of pharmacology 2006-05, Vol.537 (1), p.155-159, Article 155
Main Authors: Takeuchi, Tadayoshi, Nakamura, Aki, Nakajima, Hidemitsu, Azuma, Yasu-Taka, Hata, Fumiaki
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Alendronate
Alendronate - pharmacology
Animals
Biological and medical sciences
Bone Density Conservation Agents - pharmacology
Cholinergic Antagonists - pharmacology
Electric Stimulation
Electrical field stimulation-induced contraction
Esophageal Sphincter, Lower - drug effects
Esophageal Sphincter, Lower - physiology
Gastric Fundus - drug effects
Gastric Fundus - physiology
Ileum - drug effects
Ileum - physiology
In Vitro Techniques
Lower esophageal sphincter
Male
Medical sciences
Muscle Contraction - drug effects
NO-mediated relaxation
Pharmacology. Drug treatments
Rats
Rats, Wistar
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Summary:Alendronate is a potent inhibitor of osteoclast-mediated bone resorption, but its use results in serious esophageal damage. In order to clarify the latter, we examined the effects of alendronate on electrical field stimulation-induced responses in the rat lower esophageal sphincter. Electrical field stimulation induced atropine-sensitive contraction. Alendronate inhibited electrical field stimulation-induced contraction in a concentration-dependent manner. In the presence of N G-nitro- l-arginine ( l-nitroarginine), electrical field stimulation elicited a strong cholinergic contraction. This contraction was also inhibited by alendronate, to a similar extent as that seen in the absence of l-nitroarginine. In lower esophageal sphincter contracted by prostaglandin F 2α and treated with atropine, electrical field stimulation induced l-nitroarginine-sensitive relaxation. Alendronate did not affect relaxation. These results suggest that alendronate decreases the tone of lower esophageal sphincter by inhibiting cholinergic nervous activity.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2006.03.027