5-羟色胺_4受体在调节应激大鼠内脏敏感性中的作用

Effects of 5-hydroxytryptamine 4 receptor agonist and antagonist on visceral sensitivity and plasma serotonin level in rats under partial restraint stress

目的 研究束缚应激大鼠内脏敏感性及血浆 5 羟色胺 (5 HT)水平的改变 ,探讨 5 HT4受体激动剂和拮抗剂对束缚应激大鼠内脏高敏感性的影响及对血浆 5 HT水平的调节作用。方法 雄性Wistar大鼠 32只 ,分为对照组、应激组、5 HT4受体激动剂 (1mg/kg替加色罗 ,腹腔注射 )组和 5 HT4受体拮抗剂 (3mg/kgGR11380 8,腹腔注射 )组。以直肠内球囊扩张 (0 .4～ 1.2ml)时腹壁收缩情况代表其内脏敏感性 ,分别观察各组大鼠腹壁收缩情况 ;荧光法测定各组大鼠血浆 5 HT水平。结果 束缚应激2h后 ,应激组大鼠在各个容量直肠扩张时的腹壁收缩次数均较对照组显著增多 (0 .4ml:10 .0 0± 3.74比 6 .5 7± 1.4 0 ;0 .8ml:16 .75± 2 .92比 11.86± 3.4 4 ;1.2ml:19.5 0± 4 .2 4比 14 .86± 3.19;P <0 .0 5 ) ;应激组大鼠血浆 5 HT水平的增幅较对照组显著增高 (15 4 .6 0± 19.4 3比 97.75± 17.95 ,P <0 .0 0 1)。在 0 .4～ 1.2ml不同容量的直肠扩张时 ,5 HT4受体激动剂组的腹壁收缩次数依次为 5 .86± 2 .34、10 .5 7± 3.2 6、12 .14± 2 .91;5 HT4受体拮抗剂组依次为 3.80± 1.4 8、11.4 0± 3.2 9、12 .4 0± 2 .0 7,均较应激组显著减少 (P <0 .0 5 ,P <0 .0 1)。两者均明显降低了应激组大鼠血浆 5 HT水平的?

Objective To study the influence of partial restraint stress (PRS) on visceral sensitivity and plasma 5-hydroxytryptamine (5-HT) concentration in rats and to study the effects of 5-HT 4 receptor agonist and antagonist on visceral sensitivity and plasma 5-HT level in rats under PRS.Methods Male Wistar rats (n=32) were divided into four test groups. After two hours of PRS or sham-stress, 1-methyl-2-pyrrolidinone (solvent), tegaserod(a partial 5-HT 4 receptor agonist), and GR113808(a 5-HT 4 receptor antagonist) were administered intraperitoneally to the corresponding groups respectively. Thirty minutes after intraperitoneal injection, visceral sensitivity of rats, which was reflected by abdominal cramps induced by rectal distension, was recorded. Rectal distension was performed by insertion and inflation of a balloon(0.4-1.2 ml). Abdominal contractions were recorded by electromyography. Plasma 5-HT concentration was determined by fluorometry. Results Stress enhanced the number of abdominal cramps induced by rectal distension compared with sham-stress for all volumes of distension (0.4 ml:10.00±3.74 vs. 6.57±1.40; 0.8 ml: 16.75±2.92 vs.11.86±3.44; 1.2 ml: 19.50±4.24 vs. 14.86±3.19,P<0.05). The number of abdominal cramps for all volumes of distension in 5-HT 4 receptor agonist group is 5.86±2.34, 10.57±3.26, 12.14±2.91,and in 5-HT 4 receptor antagonist group is 3.80±1.48,11.40±3.29,12.40±2.07,both significantly decreased compared with PRS group. Stress also increased the plasma 5-HT level after rectal distension (154.60±19.43 vs. 97.75±17.95, P<0.001). 5-HT 4 receptor agonist and antagonist treatment significantly reduced the raised plasma 5-HT concentration after rectal distension under stress (113.74±13.18 vs. 154.60±19.43, P< 0.01; 47.00± 17.17 vs. 154.60±19.43, P<0.001). Conclusions Visceral hypersensitivity can be induced by stress and plasma 5-HT level raised accordingly. 5-HT 4 receptor agonist and antagonist can both reduce visceral hypersensitivity, likely via the pathway involving regulation of peripheral 5-HT release.