Sphingosine-1-phosphate and the immunosuppressant, FTY720-phosphate, regulate detrusor muscle tone.
Sphingosine-1-phosphate and the immunosuppressant, FTY720-phosphate, regulate detrusor muscle tone.
复制标题
1-磷酸鞘氨醇和免疫抑制剂 FTY720-磷酸盐可调节逼尿肌张力。
DOI：
10.1096/fj.06-7326com
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Spiegel,Sarah
中科院分区：
文献类型：
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作者：
Watterson,KennethR;Berg,KrystinaM;Kapitonov,Dmitri;Payne,ShawnG;Miner,AmyS;Bittman,Robert;Milstien,Sheldon;Ratz,PaulH;Spiegel,Sarah
膀胱过度活动综合征（OBS）是由膀胱功能紊乱引起的。膀胱平滑肌（逼尿肌）表现出独立于神经源性控制的自发节律性活动（张力），在OBS患者中增强。我们现在发现了具有生物活性的鞘鞘脂代谢产物鞘鞘苷- 1 -磷酸（S1P）在调节兔逼尿肌平滑肌张力和收缩牵拉中的重要作用。S1P诱导的逼尿肌收缩依赖于拉伸和细胞内钙。尽管逼尿肌表达S1P受体s1p1和S1P2，但似乎只有S1P2参与了S1P诱导的收缩，因为SEW2871 （S1P受体激动剂）和dihydro - S1P（除S1P2外的所有S1P受体的强效激动剂）是较差的收缩剂。与此一致，s1p2拮抗剂JTE013抑制S1P诱导的收缩。S1P介导的快速、短暂的肌肉收缩（阶段性）依赖于磷脂酶C (PLC)，而缓慢、持续的肌肉收缩（强直）则不依赖于磷脂酶C。令人惊讶的是，免疫抑制剂FTY720‐phosphate是除S1P2以外的所有S1P受体的激动剂，具有明显的收缩特性，也能诱导缓慢、持续的收缩。因此，FTY720 - phos - phate和/或S1P可能以不依赖于S1P受体的方式调节钙通道。总的来说，我们的研究结果表明S1P可能调节逼尿肌平滑肌张力，并表明复杂S1P信号的失调可能导致OBS。-Watterson， K. R., Berg， K. M., Kapitonov， D., Payne， S. G., Miner， A. S., Bittman， R., Milstien， S., Ratz， P. H., Spiegel， S.鞘氨酸- 1 -磷酸和免疫抑制剂fty720 -磷酸调节逼尿肌张力。中华医学杂志，21(2007):2818-2828。
Overactive bladder syndrome (OBS) results from disturbances of bladder function. Bladder smooth muscle (detrusor) exhibits spontaneous rhythmic activity (tone) independent of neurogenic control, which is enhanced in patients with OBS. We have now uncovered a prominent role for the bioactive sphingo‐lipid metabolite, sphingosine‐1‐phosphate (S1P), in regulating rabbit detrusor smooth muscle tone and con‐traction. S1P‐induced contraction of detrusor muscle was dependent on stretch and intracellular calcium. Although detrusor expresses the S1P receptors S1P1and S1P2, only S1P2appeared to be involved in S1P‐induced contraction, since SEW2871 (S1P1agonist) and dihydro‐S1P (potent agonist for all S1P receptors except S1P2) were poor contractile agents. In agreement, the S1P2antagonist JTE013 inhibited S1P‐induced contraction. The fast, transient muscle contraction (phasic) mediated by S1P was dependent on phospholipase C (PLC) whereas the slower, sustained contraction (tonic) was not. Surprisingly, the immunosuppressant FTY720‐phosphate, an agonist for all S1P receptors except S1P2, had distinct contractile properties and also induced slow, sustained contraction. Thus, FTY720‐phos‐phate and/or S1P may regulate calcium channels in an S1P receptor‐independent manner. Collectively, our results demonstrate that S1P may regulate detrusor smooth muscle tone and suggest that dysregulation of complex S1P signaling might contribute to OBS.—Watterson, K. R., Berg, K. M., Kapitonov, D., Payne, S. G., Miner, A. S., Bittman, R., Milstien, S., Ratz, P. H., Spiegel, S. Sphingosine‐1‐phosphate and the immuno‐suppressant, fty720‐phosphate, regulate detrusor muscle tone.FASEB J.21, 2818–2828 (2007)