Sphingosine-1-phosphate induced contraction of bladder smooth muscle

Kendig, Derek M.; Matsumoto, Alec; Moreland, Robert S.

doi:10.1016/j.ejphar.2013.10.004

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…The S1P 2 receptor induces contraction of diverse types of smooth muscle, including vascular, bronchial, intestinal, and bladder smooth muscle, by inducing increases in intracellular Ca 2+ concentration and activation of Rho/Rho kinase ( Ohmori et al, 2003 ; Hu et al, 2006 ; Kendig et al, 2013 ). In the vascular system, endothelial S1P 1 and S1P 3 receptors mediate NO-dependent vasodilation, while smooth muscle S1P 2 and S1P 3 receptors mediate vasoconstriction, with differential responses in different vascular beds ( Igarashi and Michel, 2009 ; Kerage et al, 2014 ).…”

Section: Contractile Effect Of S1p 2 In Smooth Musmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor-2 Antagonists: Therapeutic Potential and Potential Risks

et al. 2016

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The sphingosine-1-phosphate (S1P) signaling system with its specific G-protein-coupled S1P receptors, the enzymes of S1P metabolism and the S1P transporters, offers a multitude of promising targets for drug development. Until today, drug development in this area has nearly exclusively focused on (functional) antagonists at the S1P1 receptor, which cause a unique phenotype of immunomodulation. Accordingly, the first-in class S1P1 receptor modulator, fingolimod, has been approved for the treatment of relapsing-remitting multiple sclerosis, and novel S1P1 receptor (functional) antagonists are being developed for autoimmune and inflammatory diseases such as psoriasis, inflammatory bowel disease, lupus erythematodes, or polymyositis. Besides the S1P1 receptor, also S1P2 and S1P3 are widely expressed and regulate many diverse functions throughout the body. The S1P2 receptor, in particular, often exerts cellular functions which are opposed to the functions of the S1P1 receptor. As a consequence, antagonists at the S1P2 receptor have the potential to be useful in a contrasting context and different areas of indication compared to S1P1 antagonists. The present review will focus on the therapeutic potential of S1P2 receptor antagonists and discuss their opportunities as well as their potential risks. Open questions and areas which require further investigations will be emphasized in particular.

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Section: Contractile Effect Of S1p 2 In Smooth Musmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor-2 Antagonists: Therapeutic Potential and Potential Risks

et al. 2016

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“…One or more of these receptors have been reported to mediate the contractile effect of S1P in a variety of smooth muscle preparations. It has been reported that S1P-induced contractions were mediated via S1PR2 receptors in the urinary bladder [ 28 , 31 , 37 ], myometrium [ 25 ], airway smooth muscle [ 26 ], esophageal [ 27 ] and gastric smooth muscle [ 29 , 46 ]. S1P-induced contraction of gastric smooth muscle is also mediated in part by S1PR1 receptors [ 29 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…According to Chiba et al (2010), S1P-induced contraction of murine bronchial smooth muscle was abolished by Y-27632, an inhibitor of Rho kinase indicating a role for Rho-kinase pathway of calcium sensitization in S1P-induced contraction of the bronchial smooth muscle. The Rho kinase pathway of calcium sensitization has also been implicated in S1P-induced contraction of guinea-pig trachea [ 38 ], urinary bladder [ 31 , 37 ], human airway smooth muscle [ 26 ] and porcine retinal arterioles [ 51 ]. Kim et al have reported a role for the PKC pathway of calcium sensitization in S1P-induced contraction of feline esophageal smooth muscle cells [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…Sphingosine is synthesized from ceramide, a metabolic product of sphingomyeline and is phosphorylated in vivo by sphingosine kinase (SK) 1 or 2 into the S1P [ 20 ]. S1P stimulated contractions in vascular smooth muscle [ 21 – 24 ] and non-vascular smooth muscle preparations [ 25 – 31 ]. S1P also induced relaxation of vascular smooth muscles [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

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The effect of sphingosine-1-phosphate on colonic smooth muscle contractility: Modulation by TNBS-induced colitis

Al-Jarallah

Oriowo

2017

PLoS ONE

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AimIncreased levels of circulating sphingosine-1-phosphate (S1P) have been reported in ulcerative colitis. The objective of this study was to examine the effect of S1P on colonic smooth muscle contractility and how is it affected by colitis.MethodsColonic inflammation was induced by intrarectal administration of trinitrobenzene sulfonic acid. Five days later colon segments were isolated and used for contractility experiments and immunoblotting.ResultsS1P contracted control and inflamed colon segments and the contraction was significantly greater in inflamed colon segments. S1P-induced contraction was mediated by S1PR1 and S1PR2 in control and S1PR2 in inflamed colon segments. S1PR3 did not play a significant role in S1P-induced contractions in control or inflamed colon. S1PR1, S1PR2 and S1PR3 proteins were expressed in colon segments from both groups. The expression of S1PR1 and S1PR2 was significantly enhanced in control and inflamed colon segments, respectively. S1PR3 levels however were not significantly different between the two groups. Nifedipine significantly reduced S1P-induced contraction in control but not inflamed colon segments. Thapsigargin significantly reduced S1P-induced contraction of the inflamed colon. GF 109203X and Y-27632, alone abolished S1P-induced contraction of the control but not inflamed colon segments. Combination of GF 109203X, Y-27632 and thapsigargin abolished S1P-induced contraction of inflamed colon segments.ConclusionS1P contracted control colon via S1PR1 and S1PR2 and inflamed colon exclusively via S1PR2. Calcium influx (control) or release (inflamed) and calcium sensitization are involved in S1P-induced contraction. Exacerbated response to S1P in colitic colon segments may explain altered colonic motility reported in patients and experimental models of inflammatory bowel disease.

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“…Sphingosine-1-phosphate is a sphingosine signaling molecule involved in lymphoid cell migration, angiogenesis, and smooth muscle contraction. [11][12][13][14] Animal studies have suggested a role in bladder function and dysfunction. Sphingosine-1-phosphate can induce contraction of detrusor muscle strips ex vivo.…”

Section: Why This Mattersmentioning

confidence: 99%

Urinary Sphingosine-1-Phosphate as a Biomarker for Bladder Pain Syndrome

Eggers,

Crouss,

Lipetskaia

et al. 2024

UROGC

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Importance Sphingosine-1-phosphate (S1P) is a signaling molecule involved in inflammation and bladder contraction. Objectives The aims of this case-control pilot study were to compare urinary S1P concentrations in bladder pain syndrome (BPS) participants to controls and determine whether these concentrations correlate with disease severity and duration. Study Design Adult females with BPS and controls were enrolled. Bladder pain syndrome participants completed an O’Leary-Sant questionnaire. Information on duration of symptoms and treatment history was obtained. Urinary S1P and creatinine concentrations were determined. Mann-Whitney U tests were used to compare groups, and Spearman correlation was used to test for associations between concentrations and duration and severity of symptoms. Results Twenty-five participants were in each group. Median S1P concentration was 1,225 ng/dL in the BPS group and 2,183 ng/dL in the control group, which was significantly different (P < 0.0001). This difference did not persist when normalized to urinary creatinine (P = 0.58). No differences were noted in urinary S1P concentrations between treated and untreated participants (P = 0.53) or with symptom scores of 13 or greater and less than 13 (P = 0.69). Sphingosine-1-phosphate levels did not correlate with O’Leary-Sant scores (P = 0.08) or duration of symptoms (P = 0.67). Results did not change when using S1P concentrations normalized to creatinine. Conclusions This study demonstrated successful quantification of human urinary S1P concentrations. A difference in urinary S1P was found between BPS participants and controls but not when normalized to creatinine. While this is the first study to investigate urinary S1P as a biomarker for BPS, results suggest that it may have a potential role as a biomarker requiring further research.

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Sphingosine-1-phosphate induced contraction of bladder smooth muscle

Cited by 8 publications

References 36 publications

Sphingosine-1-Phosphate Receptor-2 Antagonists: Therapeutic Potential and Potential Risks

Sphingosine-1-Phosphate Receptor-2 Antagonists: Therapeutic Potential and Potential Risks

The effect of sphingosine-1-phosphate on colonic smooth muscle contractility: Modulation by TNBS-induced colitis

Urinary Sphingosine-1-Phosphate as a Biomarker for Bladder Pain Syndrome

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