Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells.
Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells.
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DOI：
10.1016/0016-5085(95)90745-9
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发表时间：
1995-12
期刊：
影响因子：
29.4
通讯作者：
J. Kuemmerle;K. Murthy;J. Grider;D. Martin;G. Makhlouf
中科院分区：
文献类型：
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作者：
J. Kuemmerle;K. Murthy;J. Grider;D. Martin;G. Makhlouf
背景与目的人类肠肌细胞上 5-羟色胺 (5-HT) 受体的类型和功能尚不清楚。通过药理学和放射性配体结合来表征 5-HT 受体。方法在分散的肌肉细胞和通过选择性受体保护仅保留一种受体类型的细胞中测量收缩、舒张、肌醇 1,4,5-三磷酸 (IP3) 和腺苷 3',5'-环单磷酸 (cAMP) 形成以及 5-HT 结合。结果 5-HT 结合完全被 5-HT 抑制，部分被 5-HT 抑制。 5-HT2A（酮色林）、5-HT4（SDZ-205,557）和 5-HT1p（N-乙酰基-5-羟基色氨酸-5-羟基色氨酸酰胺；5-HTP-DP）受体拮抗剂。 5-HT 引起的收缩被酮色林抑制，并被 SDZ-205,557 和 5-HTP-DP 增强。在酮色林存在的情况下，5-HT 会引起缩胆囊素收缩细胞的松弛，而该细胞被 SDZ-205,557 和 5-HTP-DP 抑制。 5-HT 增加 IP3（被酮色林抑制）和 cAMP（被 SDZ-205,557 和 5-HTP-DP 抑制）。在只有 5-HT2A 受体的细胞中，5-HT 仅引起收缩，残余结合被酮色林抑制。在只有5-HT45-HT1受体的细胞中，5-HT仅引起松弛，而残余结合被SDZ-205,557和5-HTP-DP抑制。结论介导收缩的5-HT2A受体和介导松弛的5-HT4受体在人肠肌细胞上共存。 5-HT4 受体与 5-HT1 受体非常相似或相同。
Background & AimsThe type and function of 5-hydroxytryptamine (5-HT) receptors on intestinal muscle cells in humans are not known. 5-HT receptors were characterized pharmacologically and by radioligand binding.MethodsContraction, relaxation, inositol 1,4,5-triphosphate (IP3) and adenosine 3′,5′-cyclic monophosphate (cAMP) formation, and 5-HT binding were measured in dispersed muscle cells and in cells in which only one receptor type was preserved by selective receptor protection.Results5-HT binding was completely inhibited by 5-HT and partially by 5-HT2A(ketanserin), 5-HT4(SDZ-205,557), and 5-HT1p(N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide; 5-HTP-DP) receptor antagonists. 5-HT caused contraction that was inhibited by ketanserin and augmented by SDZ-205,557 and 5-HTP-DP. In the presence of ketanserin, 5-HT caused relaxation of cholecystokinin-contracted cells that was inhibited by SDZ-205,557 and 5-HTP-DP. 5-HT increased IP3, which was inhibited by ketanserin, and cAMP, which was inhibited by SDZ-205,557 and 5-HTP-DP. In cells with only 5-HT2Areceptors, 5-HT caused contraction only, and residual binding was inhibited by ketanserin. In cells with only 5-HT45-HT1preceptors, 5-HT caused only relaxation and residual binding was inhibited by SDZ-205,557 and 5-HTP-DP.Conclusions5-HT2Areceptors mediating contraction and 5-HT4receptors mediating relaxation coexist on human intestinal muscle cells. The 5-HT4receptors are closely similar or identical to 5-HT1preceptors.