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Gene Review

F2rl1  -  coagulation factor II (thrombin) receptor...

Rattus norvegicus

Synonyms: Coagulation factor II receptor-like 1, PAR-2, Par-2, Par2, Proteinase-activated receptor 2, ...
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Disease relevance of F2rl1


High impact information on F2rl1


Chemical compound and disease context of F2rl1


Biological context of F2rl1

  • PAR-2 elicits afferent arteriolar vasodilation by NO-dependent and NO-independent actions [11].
  • The relative potencies of these agonists also were evaluated in two bioassays specific for the activation of rat PAR2: a cloned rat PAR2 cell calcium-signaling assay (PAR2-KNRK cells) and an aorta ring relaxation (AR) assay [12].
  • The effects of PAR2-activating PAR2-activating peptides, SLIGRL (SL)-NH2, and trans-cinnamoyl-LIGRLO (tc)-NH2 were compared with the action of trypsin, thrombin, and the PAR1 selective-activating peptide: Ala-parafluoroPhe-Arg-cyclohexylAla-Citrulline-Tyr (Cit)-NH2 for stimulating intestinal ion transport [12].
  • The lack of PAR-2-mediated platelet aggregation or smooth muscle contraction suggested it might not share the pathogenic properties associated with the thrombin receptor in the vasculature [13].
  • The purpose of this study was to determine whether thrombomodulin would alter thrombin-induced vasoconstriction, thought to be mediated predominantly by PAR-1, but not PAR-2, which mediates vascular relaxation [14].

Anatomical context of F2rl1


Associations of F2rl1 with chemical compounds

  • The PAR2-induced vasodilation was only partially blocked by NG-nitro-l-arginine methyl ester, suggesting both nitric oxide-dependent and -independent mechanisms [19].
  • The sustained component of the PAR-2-induced afferent arteriolar vasodilation was eliminated by nitric oxide (NO) synthase inhibition (100 microM nitro-L-arginine methyl ester) [11].
  • To determine whether the PAR-2 response additionally involves the electrogenic Na(+)-K(+)-ATPase, responses were evaluated in the presence of 3 mmol/l ouabain [2].
  • The synthetic peptide SLIGRL-NH(2), which corresponds to the exposed ligand sequence and selectively activates PAR-2, did not alter basal afferent arteriolar diameter but caused a concentration-dependent vasodilation (3-30 microM) of arterioles preconstricted by angiotensin II (0.1 nM) [11].
  • We demonstrated that rat peritoneal mast cells expressed PAR-1 and PAR-2 mRNA, and that PAR-2AP (tc-LIGRLO-NH(2), 1 microm) induced 64.2 +/- 4.4% specific beta-hexosaminidase release from peritoneal mast cells, whereas another PAR-2AP (SLIGRL-NH(2), 10 microM), trypsin (40 U/ml), and mast cell tryptase (1.5 microg/ml) did not [16].

Physical interactions of F2rl1

  • 6. The data obtained with the PEEV-->NETL mutation suggested: (a) that SLIGRL-NH2 and SFLLR-NH2 interact in a distinct manner with PAR2 and (b) that SFLLR-NH2 may interact differently with PAR2 than it does with PAR1 [20].

Regulatory relationships of F2rl1


Other interactions of F2rl1


Analytical, diagnostic and therapeutic context of F2rl1


  1. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Coelho, A.M., Vergnolle, N., Guiard, B., Fioramonti, J., Bueno, L. Gastroenterology (2002) [Pubmed]
  2. Redundant signaling mechanisms contribute to the vasodilatory response of the afferent arteriole to proteinase-activated receptor-2. Wang, X., Hollenberg, M.D., Loutzenhiser, R. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  3. Protease-activated receptor-2 modulates myocardial ischemia-reperfusion injury in the rat heart. Napoli, C., Cicala, C., Wallace, J.L., de Nigris, F., Santagada, V., Caliendo, G., Franconi, F., Ignarro, L.J., Cirino, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Evidence for selective effects of chronic hypertension on cerebral artery vasodilatation to protease-activated receptor-2 activation. Sobey, C.G., Moffatt, J.D., Cocks, T.M. Stroke (1999) [Pubmed]
  5. Neurogenic components of trypsin- and thrombin-induced inflammation in rat skin, in vivo. Obreja, O., Rukwied, R., Steinhoff, M., Schmelz, M. Exp. Dermatol. (2006) [Pubmed]
  6. The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection. Kawabata, A., Kinoshita, M., Nishikawa, H., Kuroda, R., Nishida, M., Araki, H., Arizono, N., Oda, Y., Kakehi, K. J. Clin. Invest. (2001) [Pubmed]
  7. Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats. Kawabata, A., Kawao, N., Itoh, H., Shimada, C., Takebe, K., Kuroda, R., Masuko, T., Kataoka, K., Ogawa, S. Neurosci. Lett. (2002) [Pubmed]
  8. Intrathecal protease-activated receptor stimulation produces thermal hyperalgesia through spinal cyclooxygenase activity. Koetzner, L., Gregory, J.A., Yaksh, T.L. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  9. Protease-activated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells. Masamune, A., Kikuta, K., Satoh, M., Suzuki, N., Shimosegawa, T. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  10. Protease-activated receptor-2-mediated contraction of urinary bladder is enhanced in cyclophosphamide-treated rats. Nakahara, T., Kubota, Y., Saito, M., Sakamoto, K., Ishii, K. Naunyn Schmiedebergs Arch. Pharmacol. (2004) [Pubmed]
  11. PAR-2 elicits afferent arteriolar vasodilation by NO-dependent and NO-independent actions. Trottier, G., Hollenberg, M., Wang, X., Gui, Y., Loutzenhiser, K., Loutzenhiser, R. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  12. Proteinase-activated receptor 2 (PAR2)-activating peptides: identification of a receptor distinct from PAR2 that regulates intestinal transport. Vergnolle, N., Macnaughton, W.K., Al-Ani, B., Saifeddine, M., Wallace, J.L., Hollenberg, M.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  13. Evidence for the presence of a proteinase-activated receptor distinct from the thrombin receptor in vascular endothelial cells. Hwa, J.J., Ghibaudi, L., Williams, P., Chintala, M., Zhang, R., Chatterjee, M., Sybertz, E. Circ. Res. (1996) [Pubmed]
  14. Vascular contraction and relaxation to thrombin and trypsin: thrombomodulin preferentially attenuates thrombin-induced contraction. Bhattacharya, A., Cohen, M.L. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  15. Four subtypes of protease-activated receptors, co-expressed in rat astrocytes, evoke different physiological signaling. Wang, H., Ubl, J.J., Reiser, G. Glia (2002) [Pubmed]
  16. Proteinase-activated receptor (PAR)-1 and -2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 and PAR-2. Stenton, G.R., Nohara, O., Déry, R.E., Vliagoftis, H., Gilchrist, M., Johri, A., Wallace, J.L., Hollenberg, M.D., Moqbel, R., Befus, A.D. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  17. Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. Saifeddine, M., al-Ani, B., Cheng, C.H., Wang, L., Hollenberg, M.D. Br. J. Pharmacol. (1996) [Pubmed]
  18. Receptor-activating peptides for PAR-1 and PAR-2 relax rat gastric artery via multiple mechanisms. Kawabata, A., Nakaya, Y., Ishiki, T., Kubo, S., Kuroda, R., Sekiguchi, F., Kawao, N., Nishikawa, H., Kawai, K. Life Sci. (2004) [Pubmed]
  19. Bidirectional regulation of renal hemodynamics by activation of PAR1 and PAR2 in isolated perfused rat kidney. Gui, Y., Loutzenhiser, R., Hollenberg, M.D. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  20. Proteinase activated receptor 2: Role of extracellular loop 2 for ligand-mediated activation. Al-Ani, B., Saifeddine, M., Kawabata, A., Hollenberg, M.D. Br. J. Pharmacol. (1999) [Pubmed]
  21. Protease-activated receptor 2 expression in trigeminal neurons innervating the rat nasal mucosa. Dinh, Q.T., Cryer, A., Dinh, S., Trevisani, M., Georgiewa, P., Chung, F., Geppetti, P., Heppt, W., Klapp, B.F., Fischer, A. Neuropeptides (2005) [Pubmed]
  22. Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland. Kawabata, A., Morimoto, N., Nishikawa, H., Kuroda, R., Oda, Y., Kakehi, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  23. Capsazepine inhibits thermal hyperalgesia but not nociception triggered by protease-activated receptor-2 in rats. Kawao, N., Shimada, C., Itoh, H., Kuroda, R., Kawabata, A. Jpn. J. Pharmacol. (2002) [Pubmed]
  24. Expression of protease-activated receptors (PARs) in OLN-93 oligodendroglial cells and mechanism of PAR-1-induced calcium signaling. Wang, Y., Richter-Landsberg, C., Reiser, G. Neuroscience (2004) [Pubmed]
  25. Four different types of protease-activated receptors are widely expressed in the brain and are up-regulated in hippocampus by severe ischemia. Striggow, F., Riek-Burchardt, M., Kiesel, A., Schmidt, W., Henrich-Noack, P., Breder, J., Krug, M., Reymann, K.G., Reiser, G. Eur. J. Neurosci. (2001) [Pubmed]
  26. Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats. Nishikawa, H., Kawai, K., Nishimura, S., Tanaka, S., Araki, H., Al-Ani, B., Hollenberg, M.D., Kuroda, R., Kawabata, A. Eur. J. Pharmacol. (2002) [Pubmed]
  27. Protease-activated receptor-2 activation improves efficiency of experimental ischemic preconditioning. Napoli, C., De Nigris, F., Cicala, C., Wallace, J.L., Caliendo, G., Condorelli, M., Santagada, V., Cirino, G. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
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