Contribution of cyclooxygenase-dependent mechanisms to contractile responses to donepezil in the rat urinary bladder.
Donepezil, an inhibitor of acetylcholinesterase, is used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease. In the present study, contractile effects of donepezil on the rat urinary bladder were examined and compared with those of the nonselective cholinesterase inhibitor neostigmine. Both donepezil and neostigmine produced concentration-dependent contractile responses of the isolated rat urinary bladder strips. The neostigmine-induced contractions were abolished by atropine. However, donepezil produced contractions of urinary bladders partly through atropine-insensitive mechanisms. The atropine-resistant component of donepezil-induced contraction was significantly reduced by the cyclooxygenase inhibitor indomethacin. These results suggest that cyclooxygenase-derived prostanoids contribute, at least in part, to contractile effects of donepezil in the rat urinary bladder.
Shimizu
Naoko
N
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Shirokane, Tokyo, Japan.
Nakahara
Tsutomu
T
Kubota
Yuko
Y
Sakamoto
Kenji
K
Ishii
Kunio
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D009388:Neostigmine; D001285:Atropine; D000077265:Donepezil; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin