5-HT decreases contractile and electrical activities in lymphatic vessels of the guinea-pig mesentery:: role of 5-HT7-receptors
5-HT decreases contractile and electrical activities in lymphatic vessels of the guinea-pig mesentery:: role of 5-HT7-receptors
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DOI：
10.1038/sj.bjp.0705264
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发表时间：
2003-05-01
影响因子：
7.3
通讯作者：
von der Weid, PY
中科院分区：
文献类型：
--
作者：
Chan, AK;von der Weid, PY
1对从豚鼠肠系膜分离的淋巴管进行体外收缩测量和细胞内微电极记录，以研究5-羟色胺（5-HT）是否影响淋巴管泵送和平滑肌膜电位。2 5-HT以浓度依赖性方式降低腔内血管灌注引起的收缩频率。在非灌注血管中，5-HT使淋巴平滑肌膜电位超极化，并降低自发性瞬时去极化（STDs）的频率和幅度5- ht7受体拮抗剂(2R)-1-[（3-羟基苯基）磺酰基]-2-[2-（4-甲基-1-哌替啶基）乙基]吡罗烷（SB269970, 0.5 muM）和5- ht1 /2/5/7受体拮抗剂甲基塞吉胺（0.5 muM）可显著逆转5- ht1 /7受体激动剂5- ct .4的作用5- ht4受体拮抗剂1-甲基- 1h -吲哚-3-羧酸[1-2-[（甲基磺酰基）氨基]乙基-4-胡椒啶基]甲酯（GR113808, 1 muM）和（1-胡椒啶基）乙基1h -吲哚-3-羧酸酯（SB203186, 1 muM）对5- ht诱导的反应无显著影响。5- ht4受体激动剂1-（4-氨基-5-氯-2-甲氧基苯基）-3-[1-（2-甲基磺酰基）乙基-4-哌啶基]1-丙酮盐盐（RS67506）降低收缩频率，但仅在50 muM时，且不影响平滑肌膜电位一氧化氮合酶抑制剂n - g -硝基l -精氨酸（100 muM）可减弱对5- HT的反应，而吲哚美辛（10 muM）和河豚毒素（1 muM）对5- HT无影响。6 . 5- ht诱导的反应被atp敏感的K+通道阻滞剂格列本脲（10 muM）和camp依赖的蛋白激酶抑制剂N-[2-（对溴氰胺）-乙基]-5-异喹啉磺酰胺-二氯胺（H89, 10 muM）抑制这些结果表明，5-羟色胺通过诱导K-ATP通道介导的平滑肌超极化和STD活性降低来调节淋巴管泵送速率，这似乎是通过激活5-羟色胺7受体偶联cAMP产生来介导的。
1 Constriction measurements and intracellular microelectrode recordings were performed in vitro on lymphatic vessels isolated from the guinea-pig mesentery to investigate whether 5-hydroxytryptamine (5-HT) affected lymphatic pumping and smooth muscle membrane potential.2 5-HT decreased in a concentration-dependent manner the frequency of constrictions induced by intraluminal vessel perfusion. In nonperfused vessels, 5-HT hyperpolarized the lymphatic smooth muscle membrane potential and decreased the frequency and amplitude of spontaneous transient depolarizations (STDs).3 The actions of 5-HT were significantly reversed by the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970, 0.5 muM) and by the 5-HT1/2/5/7 receptor antagonists methysergide (0.5 muM), and were mimicked by the 5- HT1/7-receptor agonist, 5-CT.4 The 5-HT4-receptor antagonists 1-methyl-1H-indole-3-carboxylic acid [1-2-[(methyl sulfonyl) amino] ethyl-4-piperidinyl] methyl ester (GR113808, 1 muM) and (1-piperidinyl) ethyl 1H-indole 3-carboxylate (SB203186, 1 muM) did not significantly affect the 5-HT-induced responses. The 5-HT4-receptor agonist 1-(4-amino-5-chloro-2-methoxy-phenyl)-3-[1-(2-methylsulfonylamino) ethyl-4-piperidinyl]1- propanone hydrochloride (RS67506) decreased the constriction frequency, albeit only at 50 muM and without affecting the smooth muscle membrane potential.5 Responses to 5- HT were attenuated by the nitric oxide synthase inhibitor N-G-nitro L-arginine ( 100 muM), whereas indomethacin (10 muM) and tetrodotoxin (1 muM) were without effects.6 5-HT-induced responses were inhibited by the ATP-sensitive K+ channel blocker, glibenclamide (10 muM) and the cAMP-dependent protein kinase inhibitor N-[2-(p-bromociannamylamino)-ethyl]-5-isoquinolinesulfonamide-dichloride (H89, 10 muM) blocked the hyperpolarization.7 These results suggest that 5-HT modulates the rate of lymphatic vessel pumping by eliciting K-ATP channel-mediated smooth muscle hyperpolarization and decrease in STD activity, which appear to be mediated by activation of 5-HT7 receptors coupled to cAMP production.