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 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(2alpha) 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.
Takeuchi
Tadayoshi
T
Department of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, Sakai, 599-8531, Japan. takeuchi@vet.osakafu-u.ac.jp
Nakamura
Aki
A
Nakajima
Hidemitsu
H
Azuma
Yasu-Taka
YT
Hata
Fumiaki
F
D000109:Acetylcholine / Q000494:pharmacology; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004558:Electric Stimulation; D049630:Esophageal Sphincter, Lower / Q000187:drug effects* / Q000502:physiology; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D050071:Bone Density Conservation Agents; D018680:Cholinergic Antagonists; D000109:Acetylcholine; D019386:Alendronate