Muscarinic Receptor Knockout Mice: Role of Muscarinic Acetylcholine Receptors M2, M3, and M4 in Carbamylcholine-Induced Gallbladder Contractility

摘要: Muscarinic receptors play a major role in gallbladder function, although the muscarinic receptor(s) mediating smooth muscle contractility is unclear. This study compared contractile responses to carbamylcholine (10 −7 -10 −3 M) isolated from wild-type and M 2 , 3 4 receptor knockout mice. Carbamylcholine-induced contraction was associated with tachyphylaxis release of cyclooxygenase product because indomethacin −6 inhibited carbamylcholine-induced contraction. The involved Furthermore, antagonists 11-[[[2-diethylamino- O -methyl]-1-piperidinyl]acetyl]-5,11-dihydrol-6 H -pyridol[2,3- b ][1,4]benzodiazepine-6-one (AF-DX 116) pirenzepine dextrally shifted wild-type, mice, affinities consistent interaction. In addition, maximal reduced mice for AF-DX 116 were their at receptors. shifted, or not similar may serve as an accessory protein necessary optimal potency receptor-mediated responses. Thus, provided direct unambiguous evidence that lesser extent, are predominant contractility, appear