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Natriuretic peptide receptor family C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
Natriuretic peptide receptors (provisional nomenclature) are a family of homodimeric, catalytic receptors with a single TM domain and guanylyl cyclase (EC 4.6.1.2) activity on the intracellular domain of the protein sequence. Isoforms are activated by the peptide hormones atrial natriuretic peptide (NPPA, P01160), brain natriuretic peptide (NPPB, P16860) and C-type natriuretic peptide (NPPC, P23582). Another family member is GC-C, the receptor for guanylin (GUCA2A, Q02747) and uroguanylin (GUCA2B, Q16661) . Family members have conserved ligand-binding, catalytic (guanylyl cyclase) and regulatory domains with the exception of NPR-C which has an extracellular binding domain homologous to that of other NPRs, but with a truncated intracellular domain which appears to couple, via the Gi/o family of G-proteins, to activation of phospholipase C, inwardly-rectifying potassium channels and inhibition of adenylyl cyclase activity [16].
Receptors
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GC-A (Guanylyl cyclase-A)
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GC-B (Guanylyl cyclase-B)
C
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GC-C (Guanylyl cyclase-C)
C
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NPR-C (natriuretic peptide receptor 3)
C
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Further reading
* Key recommended reading is highlighted with an asterisk
Hunt DM, Buch P, Michaelides M. (2010) Guanylate cyclases and associated activator proteins in retinal disease. Mol. Cell. Biochem., 334 (1-2): 157-68. [PMID:19941038]
Kishimoto I, Tokudome T, Nakao K, Kangawa K. (2011) Natriuretic peptide system: an overview of studies using genetically engineered animal models. FEBS J., 278 (11): 1830-41. [PMID:21477073]
Kuhn M. (2009) Function and dysfunction of mammalian membrane guanylyl cyclase receptors: lessons from genetic mouse models and implications for human diseases. Handb Exp Pharmacol, (191): 47-69. [PMID:19089325]
* Kuhn M. (2012) Endothelial actions of atrial and B-type natriuretic peptides. Br. J. Pharmacol., 166 (2): 522-31. [PMID:22220582]
Lanfear DE. (2010) Genetic variation in the natriuretic peptide system and heart failure. Heart Fail Rev, 15 (3): 219-28. [PMID:18850266]
Li P, Lin JE, Marszlowicz GP, Valentino MA, Chang C, Schulz S, Pitari GM, Waldman SA. (2009) GCC signaling in colorectal cancer: Is colorectal cancer a paracrine deficiency syndrome?. Drug News Perspect., 22 (6): 313-8. [PMID:19771320]
* Misono KS, Philo JS, Arakawa T, Ogata CM, Qiu Y, Ogawa H, Young HS. (2011) Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase. FEBS J., 278 (11): 1818-29. [PMID:21375693]
* Pandey KN. (2011) The functional genomics of guanylyl cyclase/natriuretic peptide receptor-A: perspectives and paradigms. FEBS J., 278 (11): 1792-807. [PMID:21375691]
* Potter LR. (2011) Guanylyl cyclase structure, function and regulation. Cell. Signal., 23 (12): 1921-6. [PMID:21914472]
* Potter LR. (2011) Natriuretic peptide metabolism, clearance and degradation. FEBS J., 278 (11): 1808-17. [PMID:21375692]
* Potter LR. (2011) Regulation and therapeutic targeting of peptide-activated receptor guanylyl cyclases. Pharmacol. Ther., 130 (1): 71-82. [PMID:21185863]
Potter LR, Yoder AR, Flora DR, Antos LK, Dickey DM. (2009) Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb Exp Pharmacol, (191): 341-66. [PMID:19089336]
Rubattu S, Sciarretta S, Morriello A, Calvieri C, Battistoni A, Volpe M. (2010) NPR-C: a component of the natriuretic peptide family with implications in human diseases. J. Mol. Med., 88 (9): 889-97. [PMID:20563546]
Saito Y. (2010) Roles of atrial natriuretic peptide and its therapeutic use. J Cardiol, 56 (3): 262-70. [PMID:20884176]
van Kimmenade RR, Januzzi JL. (2009) The evolution of the natriuretic peptides - Current applications in human and animal medicine. J Vet Cardiol, 11 Suppl 1: S9-21. [PMID:19285934]
References
1. Bach T, Bergholtz S, Riise J, Qvigstad E, Skomedal T, Osnes JB, Levy FO. (2014) Identification of small molecule NPR-B antagonists by high throughput screening--potential use in heart failure. Naunyn Schmiedebergs Arch. Pharmacol., 387 (1): 5-14. [PMID:24297249]
2. Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, Mahajan-Miklos S, Pierce CM, Solinga RM, Sun LJ et al.. (2010) Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur. J. Pharmacol., 649 (1-3): 328-35. [PMID:20863829]
3. Delporte C, Poloczek P, Gossen D, Tastenoy M, Winand J, Christophe J. (1991) Characterization and regulation of atrial natriuretic peptide (ANP)-R1 receptors in the human neuroblastoma cell line NB-OK-1. Eur. J. Pharmacol., 207 (1): 81-8. [PMID:1680722]
4. Deschênes J, Duperé C, McNicoll N, L'Heureux N, Auger F, Fournier A, De Léan A. (2005) Development of a selective peptide antagonist for the human natriuretic peptide receptor-B. Peptides, 26 (3): 517-24. [PMID:15652659]
5. Edelson JD, Makhlina M, Silvester KR, Vengurlekar SS, Chen X, Zhang J, Koziol-White CJ, Cooper PR, Hallam TJ, Hay DW et al.. (2013) In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide (Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH(2)) natriuretic peptide receptor-A agonist that is resistant to neutral endopeptidase and acts as a bronchodilator. Pulm Pharmacol Ther, 26 (2): 229-38. [PMID:23154072]
6. Hamra FK, Eber SL, Chin DT, Currie MG, Forte LR. (1997) Regulation of intestinal uroguanylin/guanylin receptor-mediated responses by mucosal acidity. Proc. Natl. Acad. Sci. U.S.A., 94 (6): 2705-10. [PMID:9122260]
7. Harris LA, Crowell MD. (2007) Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation. Curr. Opin. Mol. Ther., 9 (4): 403-10. [PMID:17694454]
8. Hobbs A, Foster P, Prescott C, Scotland R, Ahluwalia A. (2004) Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation, 110 (10): 1231-5. [PMID:15337698]
9. Hunt DM, Buch P, Michaelides M. (2010) Guanylate cyclases and associated activator proteins in retinal disease. Mol. Cell. Biochem., 334 (1-2): 157-68. [PMID:19941038]
10. Kambayashi Y, Nakajima S, Ueda M, Inouye K. (1989) A dicarba analog of beta-atrial natriuretic peptide (beta-ANP) inhibits guanosine 3',5'-cyclic monophosphate production induced by alpha-ANP in cultured rat vascular smooth muscle cells. FEBS Lett., 248 (1-2): 28-34. [PMID:2542088]
11. Lorget F, Kaci N, Peng J, Benoist-Lasselin C, Mugniery E, Oppeneer T, Wendt DJ, Bell SM, Bullens S, Bunting S et al.. (2012) Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. Am. J. Hum. Genet., 91 (6): 1108-14. [PMID:23200862]
12. Maack T, Suzuki M, Almeida FA, Nussenzveig D, Scarborough RM, McEnroe GA, Lewicki JA. (1987) Physiological role of silent receptors of atrial natriuretic factor. Science, 238 (4827): 675-8. [PMID:2823385]
13. Martin FL, Sangaralingham SJ, Huntley BK, McKie PM, Ichiki T, Chen HH, Korinek J, Harders GE, Burnett Jr JC. (2012) CD-NP: a novel engineered dual guanylyl cyclase activator with anti-fibrotic actions in the heart. PLoS ONE, 7 (12): e52422. [PMID:23272242]
14. Moffatt P, Thomas G, Sellin K, Bessette MC, Lafrenière F, Akhouayri O, St-Arnaud R, Lanctôt C. (2007) Osteocrin is a specific ligand of the natriuretic Peptide clearance receptor that modulates bone growth. J. Biol. Chem., 282 (50): 36454-62. [PMID:17951249]
15. Morishita Y, Sano T, Ando K, Saitoh Y, Kase H, Yamada K, Matsuda Y. (1991) Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor. Biochem. Biophys. Res. Commun., 176 (3): 949-57. [PMID:1674870]
16. Murthy KS, Makhlouf GM. (1999) Identification of the G protein-activating domain of the natriuretic peptide clearance receptor (NPR-C). J. Biol. Chem., 274 (25): 17587-92. [PMID:10364194]
17. Olson LJ, Lowe DG, Drewett JG. (1996) Novel natriuretic peptide receptor/guanylyl cyclase A-selective agonist inhibits angiotensin II- and forskolin-evoked aldosterone synthesis in a human zona glomerulosa cell line. Mol. Pharmacol., 50 (2): 430-5. [PMID:8700153]
18. Shailubhai K, Comiskey S, Foss JA, Feng R, Barrow L, Comer GM, Jacob GS. (2013) Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses. Dig. Dis. Sci., 58 (9): 2580-6. [PMID:23625291]
19. Singh G, Kuc RE, Maguire JJ, Fidock M, Davenport AP. (2006) Novel snake venom ligand dendroaspis natriuretic peptide is selective for natriuretic peptide receptor-A in human heart: downregulation of natriuretic peptide receptor-A in heart failure. Circ. Res., 99 (2): 183-90. [PMID:16778132]
20. Suga S, Nakao K, Hosoda K, Mukoyama M, Ogawa Y, Shirakami G, Arai H, Saito Y, Kambayashi Y, Inouye K. (1992) Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Endocrinology, 130 (1): 229-39. [PMID:1309330]
21. Veale CA, Alford VC, Aharony D, Banville DL, Bialecki RA, Brown FJ, Damewood JR, Dantzman CL, Edwards PD, Jacobs RT et al.. (2000) The discovery of non-basic atrial natriuretic peptide clearance receptor antagonists. Part 1. Bioorg. Med. Chem. Lett., 10 (17): 1949-52. [PMID:10987424]
22. Weber W, Fischli W, Hochuli E, Kupfer E, Weibel EK. (1991) Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity. J. Antibiot., 44 (2): 164-71. [PMID:1849131]
23. Wyss DF, Lahm HW, Manneberg M, Labhardt AM. (1991) Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments. J. Antibiot., 44 (2): 172-80. [PMID:1826288]
NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Adrian Hobbs (Co-chairperson)
Scott Waldman (Co-chairperson)
John C. Burnett, Jr.
John Garthwaite
Doris Koesling
Michaela Kuhn
Lincoln Potter
Harald Schmidt |
How to cite this family page
Database page citation:
Natriuretic peptide receptor family. Accessed on 12/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=315.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. Br J Pharmacol. 172: 5979-6023.
The polysaccharide obtained from fermentation of Aureobasidium species, HS142-1, acts as an antagonist at both NPR-A and NPR-B receptors [15].
GUCY2D (RetGC1, GC-E, Q02846) and GUCY2F (RetGC2, GC-F, P51841) are predominantly retinal guanylyl cyclase activities, which are inhibited by calcium ions acting through the guanylyl cyclase activating peptides GCAP1 (GUCA1A, 43080), GCAP2 (GUCA1B, Q9UMX6) and GCAP3 (GUCA1C, O95843) [9].