Richard M. Breyer, Ph.D.


Visit Lab Site

Faculty Appointments
Professor of Medicine Professor of BiochemistryRuth King Scoville Chair in MedicineProfessor of Pharmacology
Ph.D., Biochemistry, Massachusetts Institute of Technology, Cambridge, MassachusettsM.S., Biology, Massachusetts Institute of Technology, Cambridge, MassachusettsB.S., Microbiology, University of Michigan, Ann Arbor, Michigan
Office Address
S-3223 MCN
TN 2372
Research Description
Prostaglandin E2 (PGE2) mediates a wide range of biological effects including anti-inflammatory effects,airway resistance in asthma, fertility and maintenance of vascular tone. The precise identity of the receptors which mediate these effects are unclear. A main focus of Dr. Breyer?s research is the characterization of the molecular mechanism of action of PGE2 and determination of the structure-function relationships of the PGE2 receptors. Dr. Breyer's group is currently investigating alterations in immune/inflammatory cells function in hypertension and type 2 diabetes using both the PGE2 EP receptor knockout mice and small molecule antagonists. T

A second project in the laboratory involves using the EP3 receptors as a model system to study multiple signal transduction pathways activated by these G-protein coupled receptors. The prostaglandin EP3 receptor signals primarily through the inhibitory G-protein Gi, thereby decreasing intracellular cAMP levels, however preliminary studies have described a non-Gi coupled signal transduction pathway activated by the this receptor. Partial blockade of this novel signal transduction pathway with kinase inhibitors demonstrates that this pathway is transduced in part by a Ca++ dependent kinase pathway. Studies are underway to determine the downstream regulators which mediate this signal transduction pathway.

In addition Dr. Breyer?s lab has recently developed the technology for purifying milligram quantities of the recombinant G-protein coupled receptors. The goal of this project is to utilize this purified receptor protein to undertake biochemical characterization of the receptor protein, identify interacting proteins, and ultimately to determine the three dimensional structure of one of these receptors
Research Keywords
Structure, Function and Biology of Prostanoid Receptors. Diabetes Hypertension
Ceddia RP, Lee D, Maulis MF, Carboneau BA, Threadgill DW, Poffenberger G, Milne G, Boyd KL, Powers AC, McGuinness OP, Gannon M, Breyer RM. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice. Endocrinology [print-electronic]. 2015 Oct 10/20/2015; en20151693. PMID: 26485614, DOI: 10.1210/en.2015-1693, ISSN: 1945-7170.

Downey JD, Saleh SA, Bridges TM, Morrison RD, Daniels JS, Lindsley CW, Breyer RM. Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/1/2013; 23(1): 37-41. PMID: 23218714, PMCID: PMC3534858, PII: S0960-894X(12)01498-9, DOI: 10.1016/j.bmcl.2012.11.046, ISSN: 1464-3405.

Natarajan C, Hata AN, Hamm HE, Zent R, Breyer RM. Extracellular loop II modulates GTP sensitivity of the prostaglandin EP3 receptor. Mol. Pharmacol [print-electronic]. 2013 Jan; 83(1): 206-16. PMID: 23087260, PMCID: PMC3533480, PII: mol.112.080473, DOI: 10.1124/mol.112.080473, ISSN: 1521-0111.

Bartlett CS, Boyd KL, Harris RC, Zent R, Breyer RM. EP1 disruption attenuates end-organ damage in a mouse model of hypertension. Hypertension [print-electronic]. 2012 Nov; 60(5): 1184-91. PMID: 23006735, PMCID: PMC3478772, PII: HYPERTENSIONAHA.112.199026, DOI: 10.1161/HYPERTENSIONAHA.112.199026, ISSN: 1524-4563.

Zhou W, Dowell DR, Huckabee MM, Newcomb DC, Boswell MG, Goleniewska K, Lotz MT, Toki S, Yin H, Yao S, Natarajan C, Wu P, Sriram S, Breyer RM, Fitzgerald GA, Peebles RS. Prostaglandin I2 signaling drives Th17 differentiation and exacerbates experimental autoimmune encephalomyelitis. PLoS ONE [print-electronic]. 2012; 7(5): e33518. PMID: 22590492, PMCID: PMC3349674, PII: PONE-D-10-03779, DOI: 10.1371/journal.pone.0033518, ISSN: 1932-6203.

Swan CE, Breyer RM. Prostaglandin E2 modulation of blood pressure homeostasis: studies in rodent models. Prostaglandins Other Lipid Mediat [print-electronic]. 2011 Nov; 96(1-4): 10-3. PMID: 21801847, PMCID: PMC3208062, PII: S1098-8823(11)00050-5, DOI: 10.1016/j.prostaglandins.2011.07.001, ISSN: 1098-8823.

Jewell ML, Breyer RM, Currie KP. Regulation of calcium channels and exocytosis in mouse adrenal chromaffin cells by prostaglandin EP3 receptors. Mol. Pharmacol [print-electronic]. 2011 Jun; 79(6): 987-96. PMID: 21383044, PMCID: PMC3102550, PII: mol.110.068569, DOI: 10.1124/mol.110.068569, ISSN: 1521-0111.

Downey JD, Sanders CR, Breyer RM. Evidence for the presence of a critical disulfide bond in the mouse EP3¿ receptor. Prostaglandins Other Lipid Mediat [print-electronic]. 2011 Feb; 94(1-2): 53-8. PMID: 21236356, PMCID: PMC3065360, PII: S1098-8823(11)00006-2, DOI: 10.1016/j.prostaglandins.2010.12.007, ISSN: 1098-8823.

Howell SC, Mittal R, Huang L, Travis B, Breyer RM, Sanders CR. CHOBIMALT: a cholesterol-based detergent. Biochemistry. 2010 Nov 11/9/2010; 49(44): 9572-83. PMID: 20919740, PMCID: PMC3030671, DOI: 10.1021/bi101334j, ISSN: 1520-4995.

Smith JP, Haddad EV, Downey JD, Breyer RM, Boutaud O. PGE2 decreases reactivity of human platelets by activating EP2 and EP4. Thromb. Res [print-electronic]. 2010 Jul; 126(1): e23-9. PMID: 20451959, PMCID: PMC2902561, PII: S0049-3848(10)00228-8, DOI: 10.1016/j.thromres.2010.04.003, ISSN: 1879-2472.

Babaev VR, Chew JD, Ding L, Davis S, Breyer MD, Breyer RM, Oates JA, Fazio S, Linton MF. Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis. Cell Metab. 2008 Dec; 8(6): 492-501. PMID: 19041765, PMCID: PMC2614698, PII: S1550-4131(08)00289-1, DOI: 10.1016/j.cmet.2008.09.005, ISSN: 1932-7420.

Chen J, Zhao M, He W, Milne GL, Howard JR, Morrow J, Hébert RL, Breyer RM, Chen J, Hao CM. Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptor. Am. J. Physiol. Renal Physiol [print-electronic]. 2008 Sep; 295(3): F818-25. PMID: 18632796, PMCID: PMC2653111, PII: 90253.2008, DOI: 10.1152/ajprenal.90253.2008, ISSN: 1931-857X.

Macias-Perez IM, Zent R, Carmosino M, Breyer MD, Breyer RM, Pozzi A. Mouse EP3 alpha, beta, and gamma receptor variants reduce tumor cell proliferation and tumorigenesis in vivo. J. Biol. Chem [print-electronic]. 2008 May 5/2/2008; 283(18): 12538-45. PMID: 18230618, PMCID: PMC2335350, PII: M800105200, DOI: 10.1074/jbc.M800105200, ISSN: 0021-9258.

Guan Y, Zhang Y, Wu J, Qi Z, Yang G, Dou D, Gao Y, Chen L, Zhang X, Davis LS, Wei M, Fan X, Carmosino M, Hao C, Imig JD, Breyer RM, Breyer MD. Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting. J. Clin. Invest. 2007 Sep; 117(9): 2496-505. PMID: 17710229, PMCID: PMC1940235, DOI: 10.1172/JCI29838, ISSN: 0021-9738.

Zhou W, Blackwell TS, Goleniewska K, O'Neal JF, Fitzgerald GA, Lucitt M, Breyer RM, Peebles RS. Prostaglandin I2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells. J. Leukoc. Biol [print-electronic]. 2007 Mar; 81(3): 809-17. PMID: 17135575, PII: jlb.0606375, DOI: 10.1189/jlb.0606375, ISSN: 0741-5400.

Kamiyama M, Pozzi A, Yang L, DeBusk LM, Breyer RM, Lin PC. EP2, a receptor for PGE2, regulates tumor angiogenesis through direct effects on endothelial cell motility and survival. Oncogene [print-electronic]. 2006 Nov 11/9/2006; 25(53): 7019-28. PMID: 16732324, PII: 1209694, DOI: 10.1038/sj.onc.1209694, ISSN: 0950-9232.

Hata AN, Lybrand TP, Breyer RM. Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. J. Biol. Chem [print-electronic]. 2005 Sep 9/16/2005; 280(37): 32442-51. PMID: 16030019, PII: M502563200, DOI: 10.1074/jbc.M502563200, ISSN: 0021-9258.

Tian C, Breyer RM, Kim HJ, Karra MD, Friedman DB, Karpay A, Sanders CR. Solution NMR spectroscopy of the human vasopressin V2 receptor, a G protein-coupled receptor. J. Am. Chem. Soc. 2005 Jun 6/8/2005; 127(22): 8010-1. PMID: 15926814, DOI: 10.1021/ja051161b, ISSN: 0002-7863.

Hata AN, Lybrand TP, Marnett LJ, Breyer RM. Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol. Pharmacol [print-electronic]. 2005 Mar; 67(3): 640-7. PMID: 15563582, PII: mol.104.007971, DOI: 10.1124/mol.104.007971, ISSN: 0026-895X.

Schneider A, Guan Y, Zhang Y, Magnuson MA, Pettepher C, Loftin CD, Langenbach R, Breyer RM, Breyer MD. Generation of a conditional allele of the mouse prostaglandin EP4 receptor. Genesis. 2004 Sep; 40(1): 7-14. PMID: 15354288, DOI: 10.1002/gene.20048, ISSN: 1526-954X.

Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol. Ther. 2004 Aug; 103(2): 147-66. PMID: 15369681, PII: S0163-7258(04)00096-8, DOI: 10.1016/j.pharmthera.2004.06.003, ISSN: 0163-7258.

Pozzi A, Yan X, Macias-Perez I, Wei S, Hata AN, Breyer RM, Morrow JD, Capdevila JH. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J. Biol. Chem [print-electronic]. 2004 Jul 7/9/2004; 279(28): 29797-804. PMID: 15123663, PII: M313989200, DOI: 10.1074/jbc.M313989200, ISSN: 0021-9258.

Schneider A, Zhang Y, Zhang M, Lu WJ, Rao R, Fan X, Redha R, Davis L, Breyer RM, Harris R, Guan Y, Breyer MD. Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney. Kidney Int. 2004 Apr; 65(4): 1205-13. PMID: 15086459, DOI: 10.1111/j.1523-1755.2004.00493.x, ISSN: 0085-2538.

Breyer MD, Hébert RL, Breyer RM. Prostanoid receptors and the urogenital tract. Curr Opin Investig Drugs. 2003 Nov; 4(11): 1343-53. PMID: 14758774, ISSN: 1472-4472.

Zhang Y, Schneider A, Rao R, Lu WJ, Fan X, Davis L, Breyer RM, Breyer MD, Guan Y. Genomic structure and genitourinary expression of mouse cytosolic prostaglandin E(2) synthase gene. Biochim. Biophys. Acta. 2003 Oct 10/20/2003; 1634(1-2): 15-23. PMID: 14563409, PII: S1388198103001264, ISSN: 0006-3002.

Hata AN, Zent R, Breyer MD, Breyer RM. Expression and molecular pharmacology of the mouse CRTH2 receptor. J. Pharmacol. Exp. Ther [print-electronic]. 2003 Aug; 306(2): 463-70. PMID: 12721327, PII: jpet.103.050955, DOI: 10.1124/jpet.103.050955, ISSN: 0022-3565.

Saito O, Guan Y, Qi Z, Davis LS, Kömhoff M, Sugimoto Y, Narumiya S, Breyer RM, Breyer MD. Expression of the prostaglandin F receptor (FP) gene along the mouse genitourinary tract. Am. J. Physiol. Renal Physiol [print-electronic]. 2003 Jun; 284(6): F1164-70. PMID: 12631554, PII: 00441.2002, DOI: 10.1152/ajprenal.00441.2002, ISSN: 1931-857X.

Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, Shyr Y, Boothby M, Joyce S, Carbone DP, Breyer RM. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J. Clin. Invest. 2003 Mar; 111(5): 727-35. PMID: 12618527, PMCID: PMC151895, DOI: 10.1172/JCI16492, ISSN: 0021-9738.

Ochsner SA, Russell DL, Day AJ, Breyer RM, Richards JS. Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Endocrinology. 2003 Mar; 144(3): 1008-19. PMID: 12586778, DOI: 10.1210/en.2002-220435, ISSN: 0013-7227.

Montine TJ, Milatovic D, Gupta RC, Valyi-Nagy T, Morrow JD, Breyer RM. Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent. J. Neurochem. 2002 Oct; 83(2): 463-70. PMID: 12423256, PII: 1157, ISSN: 0022-3042.

Qi Z, Hao CM, Langenbach RI, Breyer RM, Redha R, Morrow JD, Breyer MD. Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J. Clin. Invest. 2002 Jul; 110(1): 61-9. PMID: 12093889, PMCID: PMC151026, DOI: 10.1172/JCI14752, ISSN: 0021-9738.

Guan Y, Stillman BA, Zhang Y, Schneider A, Saito O, Davis LS, Redha R, Breyer RM, Breyer MD. Cloning and expression of the rabbit prostaglandin EP2 receptor. BMC Pharmacol. 2002 Jun 6/27/2002; 2: 14. PMID: 12097143, PMCID: PMC117438, ISSN: 1471-2210.

Breyer RM, Kennedy CR, Zhang Y, Guan Y, Breyer MD. Targeted gene disruption of the prostaglandin E2 EP2 receptor. Adv. Exp. Med. Biol. 2002; 507: 321-6. PMID: 12664604, ISSN: 0065-2598.

Li, X., Pilbeam C.C., Pan, L., Breyer, R.M. , and Raisz, L.G. Effects of prostaglandin E2 on gene expression in primary osteoblastic cells from prostaglandin receptor knockout mice. Bone. 2002; 30: 567-73.

Li, X., Tomita, M., Pilbeam, C.C., Breyer, R.M., and Raisz, L.G. Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo. Prostaglandins Other Lipid Mediat. 2002; 67: 173-80.

Imig, J.D, Breyer, M.D., and Breyer, R.M. Contribution of Prostaglandin EP2 Receptors to Renal Microvascular Reactivity in Mice. Am. J. Physiol. 2002; 283: F415-F422.

Qi, Z., Hao, C.M., Langenbach, R.L., Breyer, R. M., Redha, R.D., Morrow, J.D., and Breyer, M.D. Opposite effects of cyclooxygenases-1 and -2 activity on the pressor response to angiotensin II. J.Clin.Invest. 2002; 110: 61-9.

Cheng, H.F., Wang, S.-W., Zhang, M.-Z., McKanna, J.A., Breyer, R.M., and Harris, R.C. Prostaglandins that increase rennin production in response to ACE are not mediated by EP2 or COX-1. Am. J. Physiol. 2002; 283: R638-R646.

Guan, Y., Stillman, B.A., Zhang, Y., Schneider, A., Saito, O., Davis, L.S., Redha, R., Breyer, R.M., and Breyer, M.D. Cloning and expression of the rabbit prostaglandin EP2 receptor. BMC Pharmacol. 2002; 2: 14.

Montine, T.J., Milatovic, D., Morrow, J.D., and Breyer, R.M. Lipopolysaccharide- but not kainite-induced cerebral oxidative damage is EP2 receptor dependent. J. Neurochem. 2002; 83: 463-70.

Ochsner, S.A. Russell, D.L., Day, A.J., Breyer, R.M., and Richards, J.S. Decreased expression of TNF-a stimulated gene 6 mRNA and protein in cumulus cells of the cyclooxygenase-2 knockout mouse. Endocrinology. 2002; (In Press).

Guan Y, Zhang Y, Schneider A, Riendeau D, Mancini JA, Davis L, Kömhoff M, Breyer RM, Breyer MD. Urogenital distribution of a mouse membrane-associated prostaglandin E(2) synthase. Am. J. Physiol. Renal Physiol. 2001 Dec; 281(6): F1173-7. PMID: 11704570, ISSN: 1931-857X.

Guan Y, Zhang Y, Schneider A, Davis L, Breyer RM, Breyer MD. Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature. Am. J. Physiol. Renal Physiol. 2001 Dec; 281(6): F1036-46. PMID: 11704554, ISSN: 1931-857X.

Stecenko AA, King G, Torii K, Breyer RM, Dworski R, Blackwell TS, Christman JW, Brigham KL. Dysregulated cytokine production in human cystic fibrosis bronchial epithelial cells. Inflammation. 2001 Jun; 25(3): 145-55. PMID: 11403205, ISSN: 0360-3997.

Breyer RM. Prostaglandin EP(1) receptor subtype selectivity takes shape. Mol. Pharmacol. 2001 Jun; 59(6): 1357-9. PMID: 11353793, ISSN: 0026-895X.

Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: subtypes and signaling. Annu. Rev. Pharmacol. Toxicol. 2001; 41: 661-90. PMID: 11264472, PII: 41/1/661, DOI: 10.1146/annurev.pharmtox.41.1.661, ISSN: 0362-1642.

Figueroa DJ, Breyer RM, Defoe SK, Kargman S, Daugherty BL, Waldburger K, Liu Q, Clements M, Zeng Z, O'Neill GP, Jones TR, Lynch KR, Austin CP, Evans JF. Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes. Am. J. Respir. Crit. Care Med. 2001 Jan; 163(1): 226-33. PMID: 11208650, DOI: 10.1164/ajrccm.163.1.2003101, ISSN: 1073-449X.

Breyer MD, Breyer RM. G protein-coupled prostanoid receptors and the kidney. Annu. Rev. Physiol. 2001; 63: 579-605. PMID: 11181968, PII: 63/1/579, DOI: 10.1146/annurev.physiol.63.1.579, ISSN: 0066-4278.

Figueroa, D.J., Breyer, R.M., DeFoe, S.K., Kargman, S., Daugherty, B.L., Waldburger, K., Zhizen, Z., Jones, T.R., Austin, C.P., and Evans, J.P. Expression of the cysteinyl leukotriene 1 (CysLT1) receptor in normal human lung and peripheral blood leukocytes. Am. J. Resp. Crit Care Med. 2001; 163: 226-33.

Matsumoto, H., Ma, W. Smalley, W., Trzaskos, J., Breyer, R.M., and Dey, S.K. Diversification of cyclooxygenase -2 derived prostaglandins in ovulation and implantation. Biol. Reprod. 2001; 64: 1557-65.

Stecenko, A.A., King, G., Torii, K., Breyer, R.M., Dworski, R., Blackwell, T.S., Christman, J.W., and Brigham, K.L. Dysregulated cytokine production by cultured human cystic fibrosis bronchial epithelial cells. Inflammation. 2001; 25: 145-55.

Fortner, C.N., Breyer, R.M., and Paul, R.J. EP2 Receptors Mediate Airway Relaxation To Substance P, ATP, And Prostaglandin E2. Am. J. Physiol. 2001; 281: L469-L474.

Guan, Y., Zhang, Y., Schneider, A., Davis, L., Breyer, R.M., and Breyer, M.D. Perixosome proliferator-activated receptor γ(PPARγ) activity is associated with renal microvasculature. Am. J. Physiol. 2001; 28: F1036-F1046.

Guan, Y., Zhang, Y., Schneider, A., Riendeau, D., Mancini, J.A., Davis, L., Kömhoff, M., Breyer, R.M., and Breyer, M.D. Urogenital distribution of a mouse membrane-associated prostaglandin E2 synthase. Am. J. Physiol. 2001; 281: F1173-F1177.

Breyer MD, Breyer RM. Prostaglandin E receptors and the kidney. Am. J. Physiol. Renal Physiol. 2000 Jul; 279(1): F12-23. PMID: 10894784, ISSN: 1931-857X.

Zhang Y, Guan Y, Schneider A, Brandon S, Breyer RM, Breyer MD. Characterization of murine vasopressor and vasodepressor prostaglandin E(2) receptors. Hypertension. 2000 May; 35(5): 1129-34. PMID: 10818076, ISSN: 1524-4563.

Breyer RM, Kennedy CR, Zhang Y, Breyer MD. Structure-function analyses of eicosanoid receptors. Physiologic and therapeutic implications. Ann. N. Y. Acad. Sci. 2000 Apr; 905: 221-31. PMID: 10818456, ISSN: 0077-8923.

Sheller, J. R., Mitchell, D., Meyrick, B., Oates, J. A. and Breyer, R. M. The EP2 Receptor Mediates Bronchodilation in Mice. 2000.

Zhang, Y., Guan Y., Schneider, A., Brandon, S., Breyer, R. M., and Breyer M. D. Characterization of murine vasopressor and vasodepressor prostaglandin E2 receptors. 2000.

Li, X., Okada, Y., Pilbeam C.C., Kennedy, C.R.J., Breyer, R.M. , and Raisz, L.G. Knockout of the Prostaglandin EP2 Receptor Impairs Osteoclastogenesis in vitro. 2000.

Breyer MD, Breyer RM. Prostaglandin receptors: their role in regulating renal function. Curr. Opin. Nephrol. Hypertens. 2000 Jan; 9(1): 23-9. PMID: 10654821, ISSN: 1062-4821.

Guan YF, Zhang YH, Breyer RM, Davis L, Breyer MD. Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death. Neoplasia. 1999 Oct; 1(4): 330-9. PMID: 10935488, PMCID: PMC1508103, ISSN: 1522-8002.

Stillman BA, Breyer MD, Breyer RM. Importance of the extracellular domain for prostaglandin EP(2) receptor function. Mol. Pharmacol. 1999 Sep; 56(3): 545-51. PMID: 10462542, ISSN: 0026-895X.

Audoly LP, Ma L, Feoktistov I, de Foe SK, Breyer MD, Breyer RM. Prostaglandin E-prostanoid-3 receptor activation of cyclic AMP response element-mediated gene transcription. J. Pharmacol. Exp. Ther. 1999 Apr; 289(1): 140-8. PMID: 10086997, ISSN: 0022-3565.

Kennedy CR, Zhang Y, Brandon S, Guan Y, Coffee K, Funk CD, Magnuson MA, Oates JA, Breyer MD, Breyer RM. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Nat. Med. 1999 Feb; 5(2): 217-20. PMID: 9930871, DOI: 10.1038/5583, ISSN: 1078-8956.

Kennedy, C. R. J., Zhang, Y., Brandon, S, Guan, Y., Coffee K., Funk, C. D., Magnuson, M. A., Oates, J. A., Breyer, M. D., and Breyer, R. M. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. 1999.

Audoly, L., Ma, L., Feoktistov, I. Breyer, M.D. and Breyer, R. M. EP3 receptor activation of cAMP response element mediated gene transcription. 1999.

Stillman BA, Audoly L, Breyer RM. A conserved threonine in the second extracellular loop of the human EP2 and EP4 receptors is required for ligand binding. Eur. J. Pharmacol. 1998 Sep 9/11/1998; 357(1): 73-82. PMID: 9788776, PII: S0014-2999(98)00522-6, ISSN: 0014-2999.

Breyer MD, Zhang Y, Guan YF, Hao CM, Hebert RL, Breyer RM. Regulation of renal function by prostaglandin E receptors. Kidney Int. Suppl. 1998 Sep; 67: S88-94. PMID: 9736261, ISSN: 0098-6577.

Guan Y, Zhang Y, Breyer RM, Fowler B, Davis L, Hébert RL, Breyer MD. Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor. J. Clin. Invest. 1998 Jul 7/1/1998; 102(1): 194-201. PMID: 9649573, PMCID: PMC509081, DOI: 10.1172/JCI2872, ISSN: 0021-9738.

Feoktistov I, Breyer RM, Biaggioni I. Prostanoid receptor with a novel pharmacological profile in human erythroleukemia cells. Biochem. Pharmacol. 1997 Oct 10/15/1997; 54(8): 917-26. PMID: 9354592, PII: S0006-2952(97)00288-8, ISSN: 0006-2952.

Audoly L, Breyer RM. The second extracellular loop of the prostaglandin EP3 receptor is an essential determinant of ligand selectivity. J. Biol. Chem. 1997 May 5/23/1997; 272(21): 13475-8. PMID: 9153190, ISSN: 0021-9258.

Audoly, L.P., and Breyer, R.M. The second extracellular loop of the prostaglandin EP3 receptor is an essential determinant of ligand selectivity. 1997.

Audoly L, Breyer RM. Substitution of charged amino acid residues in transmembrane regions 6 and 7 affect ligand binding and signal transduction of the prostaglandin EP3 receptor. Mol. Pharmacol. 1997 Jan; 51(1): 61-8. PMID: 9016347, ISSN: 0026-895X.

Breyer, M. D., Jacobson, H. R., Davis, L.S., and Breyer, R. M. Differential Localization of Prostaglandin E Receptor Subtypes in Human Kidney. 1996.

Breyer RM, Emeson RB, Tarng JL, Breyer MD, Davis LS, Abromson RM, Ferrenbach SM. Alternative splicing generates multiple isoforms of a rabbit prostaglandin E2 receptor. J. Biol. Chem. 1994 Feb 2/25/1994; 269(8): 6163-9. PMID: 8119961, ISSN: 0021-9258.

Breyer, R. M., Emeson, R. B., Breyer, M. D., Davis, L.S., Abromson, R.M., and Ferrenbach, S. F. Alternative Splicing Generates Multiple Isoforms of a Rabbit Prostaglandin E2 Receptor. 1994.

Breyer MD, Jacobson HR, Davis LS, Breyer RM. In situ hybridization and localization of mRNA for the rabbit prostaglandin EP3 receptor. Kidney Int. 1993 Dec; 44(6): 1372-8. PMID: 8301938, ISSN: 0085-2538.