Skip to main content
Log in

Indomethacin differentiates the renal effects of sphingosine-1-phosphate and sphingosylphosphorylcholine

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The sphingomyelin breakdown products sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) constrict intrarenal microvessels in vitro in a pertussis toxin (PTX) sensitive manner, and S1P also reduces renal blood flow in vivo. Nevertheless, both S1P and SPC have been reported to enhance diuresis and natriuresis. This pattern is similar to that of neuropeptide Y, which also reduces renal blood flow and enhances diuresis and natriuresis. The latter effects are inhibited by the cyclooxygenase inhibitor indomethacin, and various S1P and SPC responses have also been linked to the cyclooxygenase pathway. Therefore, we have investigated whether indomethacin can alter the renal effects of S1P and SPC in anaesthetised rats in vivo. In line with earlier experiments S1P bolus injections dose-dependently reduced renal blood flow (by up to 4.8±0.5 ml min−1), and this was not significantly affected by indomethacin treatment (5 mg kg−1 i.p.). Infusion of S1P but not of SPC (30 μg kg−1 min−1 each) for 60 min reduced renal blood flow by up to 0.8±0.2 ml min−1, and this was not markedly altered by indomethacin. Despite the differential renovascular effect, both S1P and SPC enhanced diuresis by up to 215±65 and 201±58 μl 15 min−1 respectively, and natriuresis by up to 25±9 and 29±11 μmol 15 min−1 respectively. While indomethacin abolished the SPC-induced diuresis and natriuresis, it, if anything, slightly enhanced the diuretic and natriuretic effect of S1P. To determine whether tubular SPC effects are receptor-mediated, PTX experiments were performed. SPC-induced enhancements of diuresis and natriuresis were abolished by PTX. We conclude that S1P, SPC and neuropeptide Y exhibit distinct patterns of modulation of renal function and that indomethacin allows such effects to be differentiated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Alewijnse AE, Michel MC (2006) Sphingosine-1-phosphate and sphingosylphosphorylcholine—two of a kind? Br J Pharmacol http://dx.doi.org/10.1038/sj.bjp.0706602

  • Alewijnse AE, Peters SLM, Michel MC (2004) Cardiovascular effects of sphingosine-1-phosphate and other sphingomyelin metabolites. Br J Pharmacol 143:666–684

    Article  PubMed  CAS  Google Scholar 

  • Bernatchez PN, Tremblay F, Rollin S, Neagoe P-E, Sirois MG (2003) Sphingosine 1-phosphate effect on endothelial cell PAF synthesis: role in cellular migration. J Cell Biochem 90:719–731

    Article  PubMed  CAS  Google Scholar 

  • Bischoff A, Michel MC (1998) Renal effects of neuropeptide Y. Pflügers Arch 435:443–453

    Article  PubMed  CAS  Google Scholar 

  • Bischoff A, Erdbrügger W, Smits J, Michel MC (1996) Neuropeptide Y-enhanced diuresis and natriuresis in anaesthetized rats is independent from renal blood flow reduction. J Physiol (Lond) 495:525–534

    CAS  Google Scholar 

  • Bischoff A, Avramidis P, Erdbrügger W, Münter K, Michel MC (1997) Receptor subtypes Y1 and Y5 are involved in the renal effects of neuropeptide Y. Br J Pharmacol 120:1335–1343

    Article  PubMed  CAS  Google Scholar 

  • Bischoff A, Limmroth V, Michel MC (1998) Indomethacin inhibits the natriuretic effects of neuropeptide Y in anesthetized rats. J Pharmacol Exp Ther 286:704–708

    PubMed  CAS  Google Scholar 

  • Bischoff A, Czyborra P, Fetscher C, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2000a) Sphingosine-1-phosphate and sphingosylphosphorylcholine constrict renal and mesenteric microvessels in vitro. Br J Pharmacol 130:1871–1877

    Article  PubMed  CAS  Google Scholar 

  • Bischoff A, Czyborra P, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2000b) Sphingosine-1-phosphate reduces rat renal and mesenteric blood flow in vivo in a pertussis toxin-sensitive manner. Br J Pharmacol 130:1878–1883

    Article  PubMed  CAS  Google Scholar 

  • Bischoff A, Finger J, Michel MC (2001a) Nifedipine inhibits sphingosine-1-phosphate-induced renovascular contraction in vitro and in vivo. Naunyn-Schmiedebergs Arch Pharmacol 364:179–182

    Article  PubMed  CAS  Google Scholar 

  • Bischoff A, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2001b) Lysosphingolipid receptor-mediated diuresis and natriuresis in anaesthetised rats. Br J Pharmacol 132:1925–1933

    Article  PubMed  CAS  Google Scholar 

  • Chalfant CE, Spiegel S (2005) Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J Cell Sci 118:4605–4612

    Article  PubMed  CAS  Google Scholar 

  • Chen PF, Chin TY, Chueh SH (1998) Ca2+ signaling induced by sphingosylphosphorylcholine and sphingosine 1-phosphate via distinct mechanisms in rat glomerular mesangial cells. Kidney Int 54:1470–1483

    Article  PubMed  CAS  Google Scholar 

  • Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G (2002) International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev 54:265–269

    Article  PubMed  CAS  Google Scholar 

  • Damirin A, Tomura H, Komachi M, Tobo M, Sato K, Mogi C, Nochi H, Tamoto K, Okajima F (2005) Sphingosine 1-phosphate receptors mediate the lipid-induced cAMP accumulation through cyclooxygenase-2/prostaglandin I2 pathway in human coronary artery smooth muscle cells. Mol Pharmacol 67:1177–1185

    Article  PubMed  CAS  Google Scholar 

  • Dantas APV, Igarashi J, Michel T (2003) Sphingosine 1-phosphate and control of vascular tone. Am J Physiol 284:H2045–H2052

    PubMed  CAS  Google Scholar 

  • Davaille J, Gallois C, Habib A, Li L, Mallat A, Tao J, Levade T, Lotersztajn S (2000) Antiproliferative properties of sphingosine 1-phosphate in human hepatic myofibroblasts. A cyclooxygenase-2 mediated pathway. J Biol Chem 275:34628–34633

    Article  PubMed  CAS  Google Scholar 

  • Hedemann J, Fetscher C, Michel MC (2004) Comparison of noradrenaline and lysosphingolipid-induced vasoconstriction in mouse and rat small mesenteric arteries. Auton Autacoid Pharmacol 24:77–85

    Article  PubMed  CAS  Google Scholar 

  • Lynch KR, Im D-S (1999) Life on the edg. Trends Pharmacol Sci 20:473–475

    Article  PubMed  CAS  Google Scholar 

  • Mathieson FA, Nixon GF (2006) Sphingolipids differentially regulate mitogen-activated protein kinases and intracellular Ca2+ in vascular smooth muscle: effects on CREB activation. Br J Pharmacol http://dx.doi.org/10.1038/sj.bjp.0706600

  • Meyer zu Heringdorf D, Himmel HM, Jakobs KH (2002) Sphingosylphosphorylcholine—biological functions and mechanisms of action. Biochim Biophys Acta 1582:178–189

    PubMed  CAS  Google Scholar 

  • Nakamura H, Takashiro Y, Hirabayashi T, Horie S, Koide Y, Nishida A, Murayama T (2004) Effects of synthetic sphingosine-1-phosphate analogs on arachidonic acid metabolism and cell death. Biochem Pharmacol 68:2187–2196

    Article  PubMed  CAS  Google Scholar 

  • Orlati S, Porcelli AM, Hrelia S, Lorenzini A, Rugolo M (1998) Intracellular calcium mobilization and phospholipid degradation in sphingosylphosphorylcholine-stimulated human airway epithelial cells. Biochem J 334:641–649

    PubMed  CAS  Google Scholar 

  • Pettus BJ, Bielawski J, Porcelli AM, Reames DL, Johnson KR, Morrow J, Chalfant CE, Obeid LM, Hannun YA (2003) The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-alpha. FASEB J 17:1411–1421

    Article  PubMed  CAS  Google Scholar 

  • Pettus BJ, Kitatani K, Chalfant CE, Taha TA, Kawamori T, Bielawski J, Obeid LM, Hannun YA (2005) The coordination of prostaglandin E2 production by sphingosine-1-phosphate and ceramide-1-phosphate. Mol Pharmacol 68:330–335

    PubMed  CAS  Google Scholar 

  • Spiegel S, Milstien S (2000) Functions of a new family of sphingosine-1-phosphate receptors. Biochim Biophys Acta 1484:107–116

    PubMed  CAS  Google Scholar 

  • Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397–407

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This work has been supported in part by a grant of the Deutsche Forschungsgemeinschaft.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin C. Michel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czyborra, C., Bischoff, A. & Michel, M.C. Indomethacin differentiates the renal effects of sphingosine-1-phosphate and sphingosylphosphorylcholine. Naunyn Schmied Arch Pharmacol 373, 37–44 (2006). https://doi.org/10.1007/s00210-006-0037-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-006-0037-6

Keywords

Navigation