Prostacyclin receptors

C.S. Chang, M. Negishi, T. Nakano, Y. Morizawa, Y. Matsumura, A. Ichikawa, 7,7-Difluoroprostacyclin derivative, AFP-07, a highly selective and potent agonist for the prostacyclin receptor. Prostaglandins 53 (1997) 83-90. 

T. Murata, F. Ushikubi, T. Matsuoka, M. Hirata, A. Yamasaki, Y. Sugimoto, A. Ichikawa, Y. Aze, T. Tanaka, N. Yoshida, A. Ueno, S. Oh-ishi, S. Narumiya, Altered pain perception and inflammatory response in mice lacking prostacyclin receptor, Nature 388 (1997) 678. 

Y. Hoshikawa, N.F. Voelkel, T. Gesell, M.D. Moore, K.G. Morris, L. Alger, S. Narumiya, M.W. Geraci, Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling. Am. J. Respir. Crit. Care Med. 164 (2001) 314. 

M. Takasuka, M. Kishi, M. Yamakawa, FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2.alpha., prostacyclin receptor agonist (carbacyclin) and their related compounds in dilute carbon tetrachloride solution Structure-activity relationships, J. Med. Chem. 37 (1994) 47. 

K.-H. Ruan, J. Wu, S.-P. So, L.A. Jenkins, Evidence of the residues involved in ligand recognition in the second extracellular loop of the prostacyclin receptor characterized by high resolution 2D NMR techniques. Arch. Biochem. Biophys. 418 (2003) 25. 

Murata T, Ushikubi F, Matsuoka T et al. (1997) Altered pain reception and inflammatory response in mice lacking prostacyclin receptor. Nature 388 678-682... 

Lawler OA, Miggin SM, KinsellaBT. Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to Gs, to Gi and to Gq-coupled effector signaling. J Biol Chem 2001 276 33,596-33,607. 

In order to determine the physiological roles of various prostanoid receptors a number of knockout mice have been developed [18]. These studies indicate that prostacyclin receptors are involved in at least some types of pain responses, EP3 receptors are involved in the development of fever, EP2 and EP4 function in allergy and bone resorption, and EPl receptors are involved in chemically induced colon cancer. The availability of cloned prostanoid receptors provides a rational and the appropriate technology to search for receptor agonists and antagonists that might provide some specificity beyond the currently available COX inhibitors, which prevent broadly the synthesis of all PGs. 

MacDermot, J., Blair, I.A. and Cresp, T.M. (1981). Prostacyclin receptors of a neuronal hybrid cell line. Divalent cations and ligand-receptor coupling. Biochem. Pharmacol, 30, 2041-2044... 

The Schollkopf reaction has found considerable use in the preparation of eompounds containing 4,5-disubstituted oxazoles. 4,5-Disubstituted oxazole 30 served as a key intermediate in DuPont s synthesis of benzamidine 31, a Factor Xa inhibitor. The Sehdllkopf reaetion has similarly found use in the preparation of 4,5-disubstituted oxazoles for P3-adrenergie receptor agonist," Fe(II)-form-selective E. coli methionine aminopeptidase inhibitor," and prostacyclin receptor antagonist programs. The robustness of this synthetic methodology has also led to the use of the Schollkopf oxazole synthesis as a test reaction in the evaluation of a number of flow-reactor systems. ... 

The Stille coupling was used in the preparation of the isocarbacyclin methyl ester derivative, an antagonist for the CNS type of prostacyclin receptors, as shown in O Fig. 41.23 (Bjorkman et al. 1998, 2000a). Since prostacyclines and prostaglandines do not cross the BBB the tracers were made as pro-drugs in the form of the corresponding methyl esters. 

Hoch M, Darpo B, Remenova T et al (2014) A thorough QT study in the context of an uptitration regimen with selexipag, a selective oral prostacyclin receptor agonist. Drug Des Devel Ther 9 175-185... 

Prostacyclin receptors (IP) mediate the effects of prostacyclin, although this is the least selective of the prostanoid receptors. Agonists, in order of relative binding affinity strength, include PGE PGF, = PGD. The effects of prostacyclin are numerous (e.g. vasodilator, hyperalgesic, inhibits platelet aggregation). The IP receptor is most closely related in sequence to the DP receptor, and most evidence indicates that IP signals via a stimulation of cAMP (Breyer et al, 2001 Ullrich et al, 2001). 

Namba T, Oida H, Sugimoto Y, Kakizuka A, Negishi M, Ichikawa A, Narumiya S. cDNA cloning of a mouse prostacyclin receptor multiple signaling pathways and expression in thymic medulla. J Biol Chem 1994 269 9986-9992. 

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