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タイトル: Muscarinic receptor subtypes involved in carbacholinduced contraction of mouse uterine smooth muscle
著者: Kitazawa, Takio
Hirama, Ryuichi
Masunaga, Kozue
Nakamura, Tatsuro
Asakawa, Koichi
Cao, Jinshan
Teraoka, Hiroki
Unno, Toshihiro
Komori, Sei-ichi
Yamada, Masahisa
Wess, Jürgen
Taneike, Tetsuro
キーワード: mouse uterus
M_2 receptor
M_3 receptor
carbachol
contraction
発行日: Jun-2008
出版者: Springer
抄録: Functional muscarinic acetylcholine receptors present in the mouse uterus were characterized by pharmacological and molecular biological studies using control (DDY and wild-type) mice, muscarinic M_2 or M_3 single receptor knockout (M_2KO, M_3KO), and M_2 and M_3 receptor double knockout mice (M_2/M_3KO). Carbachol (10 nM-100 μM) increased muscle tonus and phasic contractile activity of uterine strips of control mice in a concentration-dependent manner. The maximum carbacholinduced contractions (E_<max>) differed between cervical and ovarian regions of the uterus. The stage of the estrous cycle had no significant effect on carbachol concentration-response relationships. Tetrodotoxin did not decrease carbachol-induced contractions, but the muscarinic receptor antagonists (11-[[2-[(diethylaminomethyl)-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b[2,3-b][1,4]benzodiazepin6- one (AF-DX116), N-[2-[2-[(dipropylamino)methyl]- 1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b] [1,4] benzodiazepine-11-carboxamide (AF-DX384), 4-diphenylacetoxy-N-methyl-piperidine(4-DAMP), parafluoro- hexa hydro-sila-diphenidol (p-F-HHSiD), himbacine, methoctramine, pirenzepine, and tropicamide) inhibited carbachol-induced contractions in a competitive fashion. The pK_b values for these muscarinic receptor antagonists correlated well with the known pK_i values of these antagonists for the M_3 muscarinic receptor. In uterine strips isolated from mice treated with pertussis toxin (100 μg/kg, i.p. for 96 h), E_<max> values for carbachol were significantly decreased, but effective concentration that caused 50% of E_<max> values (EC_<50>) remained unchanged. In uterine strips treated with 4-DAMP mustard (30 nM) and AF-DX116 (1 μM), followed by subsequent washout of AF-DX116, neither carbachol nor N,N,N,-trimethyl-4- (2-oxo-1-pyrolidinyl)-2-butyn-1-ammonium iodide (oxotremorine- M) caused any contractile responses. Both M_2 and M_3 muscarinic receptor messenger RNAs were detected in the mouse uterus via reverse transcription polymerase chain reaction. Carbachol also caused contraction of uterine strips isolated from M_2KO mice, but the concentration–response curve was shifted to the right and downward compared with that for the corresponding wild-type mice. On the other hand, uterine strips isolated from M_3KO and M_2/M_3 double KO mice were virtually insensitive to carbachol. In conclusion, although both M_2 and M_3 muscarinic receptors were expressed in the mouse uterus, carbachol-induced contractile responses were predominantly mediated by the M_3 receptor. Activation of M_2 receptors alone did not cause uterine contractions; however, M_2 receptor activation enhanced M_3 receptor-mediated contractions in the mouse uterus.
URI: http://hdl.handle.net/10659/1847
ISSN: 0028-1298
著作権等: The original publication is available at www.springerlink.com
著作権リンク: http://dx.doi.org/10.1007/s00210-007-0223-1
出現コレクション:学術論文(雑誌)

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