Possible involvement of Ca2+-independent phospholipase A2 in protease-activated receptor-2-mediated contraction of rat urinary bladder

  • Yuko Kubota
  • Tsutomu Nakahara
  • Akiko Mitani
  • Takeshi Maruko
  • Maki Saito
  • Kenji Sakamoto
  • Kunio Ishii
Original Article
First Online:
Received:
Accepted:

Abstract

Possible involvement of Ca2+-independent phospholipase A2 (iPLA2) was examined in protease-activated receptor-2 (PAR-2)-mediated contraction of the rat urinary bladder. Both PAR-2 activating peptide (PAR-2 AP; SLIGRL-NH2) and trypsin produced a concentration-dependent contractile response in the urinary bladder preparations. These contractions were significantly (p<0.01) attenuated by indomethacin (10 µM), an inhibitor of cyclooxygenase, or bromoenol lactone (BEL; 10 µM), an inhibitor of iPLA2. On the other hand, the contractile responses to bradykinin were not significantly affected by BEL, although they were reduced by indomethacin. Arachidonyltrifluoromethyl ketone (AACOCF3; 30 µM), an inhibitor of cytosolic Ca2+-dependent phospholipase A2, did not affect the trypsin- and bradykinin-induced contractions. Both indomethacin and BEL had no inhibitory effect on the prostaglandin E2-induced contractions. These results suggest that PAR-2 activators and bradykinin stimulate the release of prostaglandins and thereby contract the rat urinary bladder smooth muscles. The release of prostaglandins by PAR-2 activators seems to be partly mediated by the iPLA2.

Keywords

Bradykinin Prostaglandin Protease-activated receptor-2 (PAR-2) Urinary bladder Phospholipase 
This is a preview of subscription content, log in to check access.

References

  1. Balsinde J, Winstead MV, Dennis EA (2002) Phospholipase A2 regulation of arachidonic acid mobilization. FEBS Lett 531:2–6CrossRefPubMedGoogle Scholar
  2. Briand SI, Bernier SG, Guillemette G (1996) Calcium-calmodulin plays a major role in bradykinin-induced arachidonic acid release by bovine aortic endothelial cells. J Cell Biochem 63:292–301CrossRefPubMedGoogle Scholar
  3. Brown WW, Zenser TV, Davis BB (1980) Prostaglandin E2 production by rabbit urinary bladder. Am J Physiol Renal Fluid Electrolyte Physiol 239:F452–F458Google Scholar
  4. Déry O, Corvera CU, Steinhoff M, Bunnett NW (1998) Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Physiol Cell Physiol 274:C1429–C1452Google Scholar
  5. Hollenberg MD, Compton SJ (2002) International union of pharmacology. XXVIII. Proteinase-activated receptors. Pharmacol Rev 54:203–217CrossRefPubMedGoogle Scholar
  6. Husain S, Abdel-Latif AA (1998) Role of protein kinase C alpha in endothelin-1 stimulation of cytosolic phospholipase A2 and arachidonic acid release in cultured cat iris sphincter smooth muscle cells. Biochim Biophys Acta 1392:127–144CrossRefPubMedGoogle Scholar
  7. Jeremy JY, Tsang V, Mikhailidis DP, Rogers H, Morgan RJ, Dandona P (1987) Eicosanoid synthesis by human urinary bladder mucosa: pathological implications. Br J Urol 59:36–39PubMedGoogle Scholar
  8. LaBelle EF, Polyak E (1998) Norepinephrine stimulates arachidonic acid release from vascular smooth muscle via activation of cPLA2. Am J Physiol Cell Physiol 274:C1129–C1137Google Scholar
  9. Levin RM, Wein AJ, Krasnopolsky L, Atta MA, Ghoniem GM (1995) Effect of mucosal removal on the response of the feline bladder to pharmacological stimulation. J Urol 153:1291–1294PubMedGoogle Scholar
  10. Li Q, Cathcart MK (1997) Selective inhibition of cytosolic phospholipase A2 in activated human monocytes. Regulation of superoxide anion production and low-density lipoprotein oxidation. J Biol Chem 272:2404–2411CrossRefPubMedGoogle Scholar
  11. Maggi CA, Santicioli P, Parlani M, Astolfi M, Patacchini R, Meli A (1987) The presence of mucosa reduces the contractile response of the guinea-pig urinary bladder to substance P. J Pharm Pharmacol 39:653–655PubMedGoogle Scholar
  12. Maggi CA, Patacchini R, Santicioli P, Geppetti P, Cecconi R, Giuliani S, Meli A (1989) Multiple mechanisms in the motor responses of the guinea-pig isolated urinary bladder to bradykinin. Br J Pharmacol 98:619–629PubMedGoogle Scholar
  13. McHowat J, Creer MH, Rickard A (2001) Stimulation of protease activated receptors on RT4 cells mediates arachidonic acid release via Ca2+ independent phospholipase A2. J Urol 165:2063–2067PubMedGoogle Scholar
  14. Mimata H, Tanigawa T, Ogata J, Takeshita M (1988) Regulation of prostaglandin synthesis by reduced glutathione in urinary bladder epithelium. J Urol 139:616–620PubMedGoogle Scholar
  15. Mulholland SG, Parsons CL, Shrom SH, Murphy JJ (1976) Bladder defense mechanism. Trans Am Assoc Genitourin Surg 68:83–86PubMedGoogle Scholar
  16. Nakahara T, Kubota Y, Mitani A, Maruko T, Sakamoto K, Ishii K (2003) Protease-activated receptor-2-mediated contraction in the rat urinary bladder: the role of urinary bladder mucosa. Naunyn-Schmiedebergs Arch Pharmacol 367:211–213Google Scholar
  17. Nakahata N, Nakanishi H (1988) Bradykinin-induced contraction is inhibited by tiaramide, an anti-inflammatory drug, with an inhibition of increase in intracellular free calcium. J Pharmacol Exp Ther 246:635–640PubMedGoogle Scholar
  18. Nakahata N, Ono T, Nakanishi H (1987) Contraction of prostaglandin E2 to bradykinin-induced contraction in rabbit urinary detrusor. Jpn J Pharmacol 43:351–359PubMedGoogle Scholar
  19. Parsons CL, Greenspan C, Moore SW, Mulholland SG (1977) Role of surface mucin in primary antibacterial defense of bladder. Urology 9:48–52PubMedGoogle Scholar
  20. Rickard A, McHowat J (2002) Phospholipid metabolite production in human urothelial cells after protease-activated receptor cleavage. Am J Physiol Renal Physiol 283:F944–F951PubMedGoogle Scholar
  21. Street IP, Lin HK, Laliberte F, Ghomashchi F, Wang Z, Perrier H, Tremblay NM, Huang Z, Weech PK, Gelb MH (1993) Slow- and tight-binding inhibitors of the 85-kDa human phospholipase A2. Biochemistry 32:5935–5940PubMedGoogle Scholar
  22. Trevisi L, Bova S, Cargnelli G, Ceolotto G, Luciani S (2002) Endothelin-1-induced arachidonic acid release by cytosolic phospholipase A2 activation in rat vascular smooth muscle via extracellular signal-regulated kinases pathway. Biochem Pharmacol 64:425–431CrossRefPubMedGoogle Scholar
  23. Winstead MV, Balsinde J, Dennis EA (2000) Calcium-independent phospholipase A2: structure and function. Biochim Biophys Acta 1488:28–39CrossRefPubMedGoogle Scholar
  24. Xing M, Insel PA (1996) Protein kinase C-dependent activation of cytosolic phospholipase A2 and mitogen-activated protein kinase by alpha 1-adrenergic receptors in Madin-Darby canine kidney cells. J Clin Invest 97:1302–1310PubMedGoogle Scholar
  25. Xing M, Tao L, Insel PA (1997) Role of extracellular signal-regulated kinase and PKC alpha in cytosolic PLA2 activation by bradykinin in MDCK-D1 cells. Am J Physiol Cell Physiol 272:C1380–C1387Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Yuko Kubota
    • 1
  • Tsutomu Nakahara
    • 1
  • Akiko Mitani
    • 1
  • Takeshi Maruko
    • 1
  • Maki Saito
    • 1
  • Kenji Sakamoto
    • 1
  • Kunio Ishii
    • 1
  1. 1.Department of Molecular PharmacologyKitasato University School of Pharmaceutical SciencesMinato-ku, TokyoJapan

Personalised recommendations