Read Kate E, Sanger Gareth J, Ramage Andrew G
Department of Pharmacology, University College London, Royal Free Campus, Hampstead, London NW3 2PF.
Br J Pharmacol. 2003 Sep;140(1):53-60. doi: 10.1038/sj.bjp.0705399. Epub 2003 Jul 29.
(1) The effects of the selective 5-HT7 receptor antagonists SB-269970 (3-300 microg kg-1; n=5-6) and SB-656104 (30 microg kg-1; n=5) administered centrally (i.c.v.) were investigated on the 'micturition reflex' in the urethane anaesthetized female rat. (2) In cystometric recordings, SB-269970 caused significant increases in volume of 58+/-15 and 138+/-33% and pressure of 140+/-46 and 149+/-60% thresholds at 10 and 30 microg kg-1. These changes were associated with significant decreases in distension-induced bladder contraction of 62+/-14 and 60+/-11%, respectively. However, there was no change in residual volume. At the higher doses, SB-269970 blocked the micturition reflex. SB-656104 had similar effects to SB-269970 but in addition significantly increased the residual volume. (3) SB-269970 (10 microg kg-1; n=5) given i.v. had no effect on the micturition reflex. (4) SB-269970 (30 microg kg-1; n=4) given intrathecally (i.t.) had no effect on micturition reflex, although the selective 5-HT1A receptor antagonist WAY-100635 given i.t. after SB-269970 caused a significant increase in the volume threshold. (5) Using an isovolumetric method in which urethral changes were measured, SB-269970 (30 microg kg-1; n=4; i.c.v.) failed to have any effect on these urethral-evoked changes although they significantly reduced the amplitude of the bladder contraction. (6) These data demonstrate that 5-HT7 receptors located supraspinally in the rat are involved in the control of micturition.
(1) 研究了选择性5-羟色胺7（5-HT7）受体拮抗剂SB-269970（3 - 300微克/千克；n = 5 - 6）和SB-656104（30微克/千克；n = 5）经脑室内（i.c.v.）给药对乌拉坦麻醉的雌性大鼠“排尿反射”的影响。(2) 在膀胱测压记录中，SB-269970在10和30微克/千克剂量时，使容量阈值显著增加了58±15%和138±33%，压力阈值增加了140±46%和149±60%。这些变化分别伴随着扩张诱导的膀胱收缩显著减少62±14%和60±11%。然而，残余尿量没有变化。在较高剂量时，SB-269970阻断了排尿反射。SB-656104具有与SB-269970相似的作用，但此外还显著增加了残余尿量。(3) 静脉内（i.v.）给予SB-269970（10微克/千克；n = 5）对排尿反射没有影响。(4) 鞘内（i.t.）给予SB-269970（30微克/千克；n = 4）对排尿反射没有影响，尽管在SB-269970之后鞘内给予选择性5-HT1A受体拮抗剂WAY-100635使容量阈值显著增加。(5) 使用等容方法测量尿道变化，SB-269970（30微克/千克；n = 4；i.c.v.）对这些尿道诱发的变化没有任何影响，尽管它们显著降低了膀胱收缩的幅度。(6) 这些数据表明，大鼠脊髓以上部位的5-HT7受体参与排尿控制。
