Leclere P G, Prins N H, Schuurkes J A J, Lefebvre R A
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Neurogastroenterol Motil. 2005 Jun;17(3):366-75. doi: 10.1111/j.1365-2982.2005.00621.x.
5-Hydroxytryptamine 4 (5-HT4) receptor agonists promote colonic propulsion. The alteration of circular muscle (CM) motility underlying this involves inhibition of contractility via smooth muscle 5-HT4 receptors and proximal colonic motility stimulation, the mechanism of the latter not having been characterized. Our aim was to identify and characterize a 5-HT4 receptor-mediated stimulation of human colon CM contractile activity. 5-HT4 receptor ligands were tested on electrical field stimulation (EFS)-induced contractions of human colonic muscle strips cut in the circular direction (called 'whole tissue' strips). Additionally, after incubation of tissues with [3H]-choline these compounds were tested on EFS-induced release of tritium in whole tissue strips and in 'isolated' CM strips, obtained by superficial cutting in the CM layer. Tetrodotoxin and atropine blocked EFS-induced contractions of whole tissue CM strips. Prucalopride (0.3 micromol L-1) evoked a heterogenous response on EFS-induced contraction, ranging from inhibition (most frequently observed) to enhancement. In the release experiments, EFS-induced tritium efflux was blocked by tetrodotoxin. Prucalopride increased EFS-induced tritium and [3H]-acetylcholine efflux in whole tissue and in isolated CM strips. All effects of prucalopride were antagonized by the selective 5-HT4 receptor antagonist GR113808. The results obtained indicate the presence of excitatory 5-HT4 receptors on cholinergic nerves within the CM of human colon.
5-羟色胺4（5-HT4）受体激动剂可促进结肠推进。其背后环形肌（CM）运动的改变涉及通过平滑肌5-HT4受体抑制收缩性以及刺激结肠近端运动，后者的机制尚未明确。我们的目的是识别和表征5-HT4受体介导的对人结肠CM收缩活性的刺激作用。在沿环形方向切割的人结肠肌条（称为“全组织”条）上，测试5-HT4受体配体对电场刺激（EFS）诱导的收缩的影响。此外，在用[3H]-胆碱孵育组织后，在全组织条和通过在CM层进行浅表切割获得的“分离的”CM条上测试这些化合物对EFS诱导的氚释放的影响。河豚毒素和阿托品可阻断EFS诱导的全组织CM条的收缩。普芦卡必利（0.3 μmol L-1）对EFS诱导的收缩产生异质性反应，范围从抑制（最常观察到）到增强。在释放实验中，河豚毒素可阻断EFS诱导的氚外流。普芦卡必利可增加全组织和分离的CM条中EFS诱导的氚和[3H]-乙酰胆碱外流。普芦卡必利的所有作用均被选择性5-HT4受体拮抗剂GR113808拮抗。所得结果表明人结肠CM内胆碱能神经上存在兴奋性5-HT4受体。
