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PTGIR  -  prostaglandin I2 (prostacyclin) receptor (IP)

Homo sapiens

Synonyms: IP, PGI receptor, PGI2 receptor, PRIPR, Prostacyclin receptor, ...
 
 
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Disease relevance of PTGIR

 

High impact information on PTGIR

  • The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP [7].
  • Indomethacin (1, 5, and 10 mg/kg, IP, -30 minutes) induced a dose-related prevention of the inhibitory effect of IC interleukin-1 beta [8].
  • The IP receptor mRNA is highly expressed near the glomerulus, in the afferent arteriole, where it may also dilate renal arterioles and stimulate renin release [9].
  • PGI2, the primary endogenous agonist for the IP receptor, is rapidly produced following tissue injury or inflammation; thus, it may be of equal, or greater, importance than PGE2 during episodes of inflammatory pain [10].
  • Prostacyclin (PGI2) has been traditionally regarded as an important regulator of haemostasis, mediating its effects through prostacyclin (IP) receptors coupled to adenylate cyclase [11].
 

Chemical compound and disease context of PTGIR

 

Biological context of PTGIR

  • The PTGER1, TBXA2R, and PTGIR genes mapped to chromosome 19 at positions 19p13.1, 19p13.3, and 19q13.3, respectively [13].
  • Thus, we conclude that TPalpha, but not TPbeta, is subject to cross-desensitization by IP mediated through direct protein kinase A phosphorylation at Ser(329) and propose that TPalpha may be the isoform physiologically relevant to TP:IP-mediated vascular hemostasis [14].
  • Expression of the immunoreactive IP receptor protein was greatest during the proliferative and early secretory phases of the menstrual cycle [15].
  • The effect of the farnesyl protein transferase inhibitor SCH66336 on isoprenylation and signalling by the prostacyclin receptor [16].
  • Over the last decade, mutagenesis studies of the IP receptor, in conjunction with in vitro functional assays and molecular modeling, have provided critical insights into the molecular mechanisms of both agonist binding and receptor activation [2].
 

Anatomical context of PTGIR

 

Associations of PTGIR with chemical compounds

 

Co-localisations of PTGIR

  • Furthermore, EGFR colocalized with IP receptor in the glandular epithelial compartment [15].
 

Regulatory relationships of PTGIR

  • These data suggest that PGI-IP interaction within glandular epithelial cells can promote the expression of proangiogenic genes in human endometrium via cross talk with the EGFR [15].
  • Treatment of cells with lipopolysaccharide (LPS)/interferon gamma (IFN-gamma) further enhanced the IP receptor mRNA expression 2.7 +/- 0.1-fold above basal levels (n = 6) [21].
  • The IP receptor messenger RNA is most highly expressed in the afferent arteriole and it may also modulate renal arterial resistance and renin release [22].
  • HAS2 mRNA levels were also stimulated by a selective prostacyclin receptor (IP) agonist, cicaprost (10 nmol/L), prostaglandin E(2) (10 nmol/L), and the EP(2) receptor agonist, butaprost (1 micromol/L) [23].
 

Other interactions of PTGIR

  • In HEK 293 cells, signaling by TPalpha, but not TPbeta, was subject to IP-mediated desensitization in a protein kinase A-dependent, protein kinase C-independent manner [14].
  • Pretreatment with either statin significantly reduced IP receptor mediated desensitization of signalling by the h.TPalpha, but not by the h.TPbeta, receptor isoform [20].
  • The IP receptor, which binds prostacyclin and couples to stimulation of adenylyl cyclase, and three isoforms of the inhibitory EP3 receptor were equally expressed in platelets, HEL cells and umbilical artery smooth muscle cells [24].
  • AIMS: This study was designed to investigate the influence of prostacyclin receptor (IP receptor) activation on iNOS expression and NO formation in human peripheral blood monocytes [21].
  • Although 12-iso-PGF2alpha caused a dose-dependent activation of the FP, it failed to activate the recombinant human prostacyclin receptor and caused only minimal activation of the thromboxane receptor isoforms stably expressed in HEK 293 cells [25].
 

Analytical, diagnostic and therapeutic context of PTGIR

References

  1. Prostacyclin receptor induces STAT1 and STAT3 phosphorylations in human erythroleukemia cells: a mechanism requiring PTX-insensitive G proteins, ERK and JNK. Lo, R.K., Wise, H., Wong, Y.H. Cell. Signal. (2006) [Pubmed]
  2. Human prostacyclin receptor structure and function from naturally-occurring and synthetic mutations. Stitham, J., Arehart, E.J., Gleim, S.R., Douville, K.L., Hwa, J. Prostaglandins Other Lipid Mediat. (2007) [Pubmed]
  3. Impaired receptor binding and activation associated with a human prostacyclin receptor polymorphism. Stitham, J., Stojanovic, A., Hwa, J. J. Biol. Chem. (2002) [Pubmed]
  4. Expression of prostanoid receptors in human ductus arteriosus. Leonhardt, A., Glaser, A., Wegmann, M., Schranz, D., Seyberth, H., Nüsing, R. Br. J. Pharmacol. (2003) [Pubmed]
  5. Cardioprotective prostacyclin signaling in vascular smooth muscle. Fetalvero, K.M., Martin, K.A., Hwa, J. Prostaglandins Other Lipid Mediat. (2007) [Pubmed]
  6. Differential association between human prostacyclin receptor polymorphisms and the development of venous thrombosis and intimal hyperplasia: a clinical biomarker study. Patrignani, P., Di Febbo, C., Tacconelli, S., Douville, K., Guglielmi, M.D., Horvath, R.J., Ding, M., Sierra, K., Stitham, J., Gleim, S., Baccante, G., Moretta, V., Di Francesco, L., Capone, M.L., Porreca, E., Hwa, J. Pharmacogenet. Genomics (2008) [Pubmed]
  7. Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients. Stratton, R., Shiwen, X., Martini, G., Holmes, A., Leask, A., Haberberger, T., Martin, G.R., Black, C.M., Abraham, D. J. Clin. Invest. (2001) [Pubmed]
  8. Central action of recombinant interleukin-1 to inhibit acid secretion in rats. Saperas, E.S., Yang, H., Rivier, C., Taché, Y. Gastroenterology (1990) [Pubmed]
  9. G protein-coupled prostanoid receptors and the kidney. Breyer, M.D., Breyer, R.M. Annu. Rev. Physiol. (2001) [Pubmed]
  10. The role of IP prostanoid receptors in inflammatory pain. Bley, K.R., Hunter, J.C., Eglen, R.M., Smith, J.A. Trends Pharmacol. Sci. (1998) [Pubmed]
  11. Focus on prostacyclin and its novel mimetics. Wise, H., Jones, R.L. Trends Pharmacol. Sci. (1996) [Pubmed]
  12. Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat. Gordon, C.J. Pharmacol. Biochem. Behav. (1996) [Pubmed]
  13. Chromosomal localization of the human prostanoid receptor gene family. Duncan, A.M., Anderson, L.L., Funk, C.D., Abramovitz, M., Adam, M. Genomics (1995) [Pubmed]
  14. The alpha, but not the beta, isoform of the human thromboxane A2 receptor is a target for prostacyclin-mediated desensitization. Walsh, M.T., Foley, J.F., Kinsella, B.T. J. Biol. Chem. (2000) [Pubmed]
  15. Prostacyclin receptor up-regulates the expression of angiogenic genes in human endometrium via cross talk with epidermal growth factor Receptor and the extracellular signaling receptor kinase 1/2 pathway. Smith, O.P., Battersby, S., Sales, K.J., Critchley, H.O., Jabbour, H.N. Endocrinology (2006) [Pubmed]
  16. The effect of the farnesyl protein transferase inhibitor SCH66336 on isoprenylation and signalling by the prostacyclin receptor. O'Meara, S.J., Kinsella, B.T. Biochem. J. (2005) [Pubmed]
  17. Developmental regulation of prostacyclin synthase and prostacyclin receptors in the ovine uterus and conceptus during the peri-implantation period. Cammas, L., Reinaud, P., Bordas, N., Dubois, O., Germain, G., Charpigny, G. Reproduction (2006) [Pubmed]
  18. Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system. Nakagawa, O., Tanaka, I., Usui, T., Harada, M., Sasaki, Y., Itoh, H., Yoshimasa, T., Namba, T., Narumiya, S., Nakao, K. Circulation (1994) [Pubmed]
  19. Expression of prostacyclin receptor in human megakaryocytes. Sasaki, Y., Takahashi, T., Tanaka, I., Nakamura, K., Okuno, Y., Nakagawa, O., Narumiya, S., Nakao, K. Blood (1997) [Pubmed]
  20. The effects of the statins lovastatin and cerivastatin on signalling by the prostanoid IP-receptor. Lawler, O.A., Miggin, S.M., Kinsella, B.T. Br. J. Pharmacol. (2001) [Pubmed]
  21. Prostacyclin enhances the expression of LPS/INF-gamma-induced nitric oxide synthase in human monocytes. Plum, J., Huang, C., Grabensee, B., Schrör, K., Meyer-Kirchrath, J. Nephron (2002) [Pubmed]
  22. Prostaglandin receptors: their role in regulating renal function. Breyer, M.D., Breyer, R.M. Curr. Opin. Nephrol. Hypertens. (2000) [Pubmed]
  23. Induction of hyaluronic acid synthase 2 (HAS2) in human vascular smooth muscle cells by vasodilatory prostaglandins. Sussmann, M., Sarbia, M., Meyer-Kirchrath, J., Nüsing, R.M., Schrör, K., Fischer, J.W. Circ. Res. (2004) [Pubmed]
  24. Distribution of prostaglandin IP and EP receptor subtypes and isoforms in platelets and human umbilical artery smooth muscle cells. Paul, B.Z., Ashby, B., Sheth, S.B. Br. J. Haematol. (1998) [Pubmed]
  25. Functional characterization of the ocular prostaglandin f2alpha (PGF2alpha) receptor. Activation by the isoprostane, 12-iso-PGF2alpha. Kunapuli, P., Lawson, J.A., Rokach, J., FitzGerald, G.A. J. Biol. Chem. (1997) [Pubmed]
  26. A strategy using NMR peptide structures of thromboxane A2 receptor as templates to construct ligand-recognition pocket of prostacyclin receptor. Ruan, C.H., Wu, J., Ruan, K.H. BMC Biochem. (2005) [Pubmed]
 
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