Dr Janet Maguire

University position

Senior Research Associate

Dr Janet Maguire is pleased to consider applications from prospective PhD students.

Departments

Department of Medicine

Institutes

Clinical Pharmacology Unit

Home page

http://www-davenport.medschl.cam.ac.uk/

Research Themes

Systems and Computational Neuroscience

Cellular and Molecular Neuroscience

Interests

The aim of our research is to identify the function of G-protein coupled receptors and their ligands in the human cerebrovascular system in health and disease. The majority of research output has focussed on a family of three bioactive peptides, the endothelins, to understand the pharmacology of these important vasoactive mediators and their receptors in human health and disease (e.g atherosclerosis, stroke). With the sequencing of the human genome, our group has been exploiting the wealth of novel protein information to investigate the potential role of newly identified G-protein coupled receptors – the ‘orphan’ receptors, so called because their endogenous ligands are not yet known. As these are paired with ligands by reverse pharmacology, we have been systematically determining the localisation and function of these new chemical messengers in human cerebrovascular tissues to provide evidence of novel transmitter systems that may subsequently be exploited as drug targets.

Research Focus

Keywords

G-protein coupled receptors

endothelin

vasoactive peptides

human pharmacology

orphan GPCR

Clinical conditions

Atherosclerosis

Hypertension

Stroke

Equipment

Confocal microscopy

Human in vitro vascular pharmacology

Immunohistochemistry

Receptor binding and autoradiography

Collaborators

No collaborators listed

Associated News Items


    Key publications

    Clarke MCH, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD, Bennett MR (2006), “Apoptosis of vascular smooth muscle cells is silent in normal arteries, but induces vulnerable plaques in atherosclerosis” Nature Medicine 12:1075-1080

    Maguire JJ, Wiley KE, Kuc RE, Stoneman VEA, Bennett MR, Davenport AP (2006), “Endothelin-mediated vasoconstriction in early atherosclerosis is markedly increased in ApoE-/- mouse but prevented by atorvastatin” Exper Biol Med 231:806-812

    Singh G, Maguire JJ, Kuc RE, Fidock M, Davenport AP (2004), “ Identification and cellular localisation of NPW1 (GPR7) receptors for the novel neuropeptide W-23 by [125I]-NPW radioligand binding and immunocytochemistry” Br Res 1017(1-2):222-226 Details

    Publications

    2014

    Kuc RE, Carlebur M, Maguire JJ, Yang P, Long L, Toshner M, Morrell NW, Davenport AP (2014), “Modulation of endothelin receptors in the failing right ventricle of the heart and vasculature of the lung in human pulmonary arterial hypertension.” Life Sci Details

    2013

    Ling L, Maguire JJ, Davenport AP (2013), “Endothelin-2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer.” Br J Pharmacol 168(2):283-95 Details

    Zheng Y, Humphry M, Maguire JJ, Bennett MR, Clarke MC (2013), “Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation.” Immunity 38(2):285-95 Details

    2012

    Ling L, Kuc RE, Maguire JJ, Davie NJ, Webb DJ, Gibbs P, Alexander GJ, Davenport AP (2012), “Comparison of endothelin receptors in normal versus cirrhotic human liver and in the liver from endothelial cell-specific ETB knockout mice.” Life Sci 91(13-14):716-22 Details

    Maguire JJ, Kuc RE, Davenport AP (2012), “Radioligand binding assays and their analysis.” Methods Mol Biol 897:31-77 Details

    Maguire JJ, Kuc RE, Davenport AP (2012), “Defining the affinity and receptor sub-type selectivity of four classes of endothelin antagonists in clinically relevant human cardiovascular tissues.” Life Sci 91(13-14):681-6 Details

    Maguire JJ, Kuc RE, Pell VR, Green A, Brown M, Kumar S, Wehrman T, Quinn E, Davenport AP (2012), “Comparison of human ETA and ETB receptor signalling via G-protein and β-arrestin pathways.” Life Sci 91(13-14):544-9 Details

    2011

    Davenport AP, Maguire JJ (2011), “Pharmacology of renal endothelin receptors.” Contrib Nephrol 172:1-17 Details

    Jones KL, Maguire JJ, Davenport AP (2011), “Chemokine receptor CCR5: from AIDS to atherosclerosis.” Br J Pharmacol 162(7):1453-69 Details

    Macaluso NJ, Pitkin SL, Maguire JJ, Davenport AP, Glen RC (2011), “Discovery of a Competitive Apelin Receptor (APJ) Antagonist.” ChemMedChem 6(6):1017-23 Details

    Maguire JJ, Kirby HR, Mead EJ, Kuc RE, d'Anglemont de Tassigny X, Colledge WH, Davenport AP (2011), “Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor.” PLoS One 6(11):e27601 Details

    2010

    Johnström P, Fryer TD, Richards HK, Maguire JJ, Clark JC, Pickard JD, Davenport AP (2010), “Positron emission tomography of [18F]-big endothelin-1 reveals renal excretion but tissue-specific conversion to [18F]-endothelin-1 in lung and liver.” Br J Pharmacol 159(4):812-9 Details

    Kelland NF, Kuc RE, McLean DL, Azfer A, Bagnall AJ, Gray GA, Gulliver-Sloan FH, Maguire JJ, Davenport AP, Kotelevtsev YV, Webb DJ (2010), “Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1.” Can J Physiol Pharmacol 88(6):644-51 Details

    Kirby HR, Maguire JJ, Colledge WH, Davenport AP (2010), “International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function.” Pharmacol Rev 62(4):565-78 Details

    Mitchell JD, Kuc RE, Maguire JJ, Davenport AP (2010), “Evidence for a novel vasospastic transmitter system, neuromedin U, in the equine digital circulation.” Vet J 186(1):106-9 Details

    Pitkin SL, Maguire JJ, Bonner TI, Davenport AP (2010), “International Union of Basic and Clinical Pharmacology. LXXIV. Apelin receptor nomenclature, distribution, pharmacology, and function.” Pharmacol Rev 62(3):331-42 Details

    Pitkin SL, Maguire JJ, Kuc RE, Davenport AP (2010), “Modulation of the apelin/APJ system in heart failure and atherosclerosis in man.” Br J Pharmacol 160(7):1785-95 Details

    2009

    Maguire JJ, Kleinz MJ, Pitkin SL, Davenport AP (2009), “[Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease.” Hypertension 54(3):598-604 Details

    Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP (2009), “International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature.” Pharmacol Rev 61(1):1-8 Details

    Mitchell JD, Maguire JJ, Davenport AP (2009), “Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S.” Br J Pharmacol 158(1):87-103 Details

    Mitchell JD, Maguire JJ, Kuc RE, Davenport AP (2009), “Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system.” Cardiovasc Res 81(2):353-61 Details

    2008

    Clarke MC, Littlewood TD, Figg N, Maguire JJ, Davenport AP, Goddard M, Bennett MR (2008), “Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration.” Circ Res 102(12):1529-38 Details

    Maguire JJ, Kuc RE, Kleinz MJ, Davenport AP (2008), “Immunocytochemical localization of the urotensin-II receptor, UT, to rat and human tissues: relevance to function.” Peptides 29(5):735-42 Details

    2007

    Mead EJ, Maguire JJ, Kuc RE, Davenport AP (2007), “Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system.” Br J Pharmacol 151(8):1143-53 Details

    Mead EJ, Maguire JJ, Kuc RE, Davenport AP (2007), “Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels.” Endocrinology 148(1):140-7 Details

    2006

    Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD, Bennett MR (2006), “Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis.” Nat Med 12(9):1075-80 Details

    Davenport AP, Maguire JJ (2006), “Endothelin.” Handb Exp Pharmacol (176 Pt 1):295-329 Details

    Kleinz MJ, Maguire JJ, Skepper JN, Davenport AP (2006), “Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man.” Cardiovasc Res 69(1):227-35 Details

    Kuc RE, Maguire JJ, Davenport AP (2006), “Quantification of endothelin receptor subtypes in peripheral tissues reveals downregulation of ET(A) receptors in ET(B)-deficient mice.” Exp Biol Med (Maywood) 231(6):741-5 Details

    Maguire JJ, Wiley KE, Kuc RE, Stoneman VE, Bennett MR, Davenport AP (2006), “Endothelin-mediated vasoconstriction in early atherosclerosis is markedly increased in ApoE-/- mouse but prevented by atorvastatin.” Exp Biol Med (Maywood) 231(6):806-12 Details

    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 Details

    Singh G, Maguire JJ, Kuc RE, Skepper JN, Fidock M, Davenport AP (2006), “Characterization of the snake venom ligand [125I]-DNP binding to natriuretic peptide receptor-A in human artery and potent DNP mediated vasodilatation.” Br J Pharmacol 149(7):838-44 Details

    2005

    Maguire JJ, Davenport AP (2005), “Regulation of vascular reactivity by established and emerging GPCRs.” Trends Pharmacol Sci 26(9):448-54 Details

    2004

    Maguire JJ, Kuc RE, Wiley KE, Kleinz MJ, Davenport AP (2004), “Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries.” Peptides 25(10):1767-74 Details

    2003

    Maguire JJ (2003), “Discovering orphan receptor function using human in vitro pharmacology.” Curr Opin Pharmacol 3(2):135-9 Details

    2002

    Davenport AP, Maguire JJ (2002), “Of mice and men: advances in endothelin research and first antagonist gains FDA approval.” Trends Pharmacol Sci 23(4):155-7 Details

    Katugampola SD, Kuc RE, Maguire JJ, Davenport AP (2002), “G-protein-coupled receptors in human atherosclerosis: comparison of vasoconstrictors (endothelin and thromboxane) with recently de-orphanized (urotensin-II, apelin and ghrelin) receptors.” Clin Sci (Lond) 103 Suppl 48:171S-175S Details

    Katugampola SD, Maguire JJ, Kuc RE, Wiley KE, Davenport AP (2002), “Discovery of recently adopted orphan receptors for apelin, urotensin II, and ghrelin identified using novel radioligands and functional role in the human cardiovascular system.” Can J Physiol Pharmacol 80(5):369-74 Details

    Maguire JJ (2002), “Endothelin-converting enzyme activity in vascular smooth muscle preparations in vitro.” Methods Mol Biol 206:165-77 Details

    Maguire JJ, Davenport AP (2002), “Is urotensin-II the new endothelin?” Br J Pharmacol 137(5):579-88 Details

    Maguire JJ, Yu JC, Davenport AP (2002), “ETA receptor antagonists inhibit intimal smooth muscle cell proliferation in human vessels.” Clin Sci (Lond) 103 Suppl 48:184S-188S Details

    Télémaque-Potts S, Kuc RE, Maguire JJ, Ohlstein E, Yanagisawa M, Davenport AP (2002), “Elevated systemic levels of endothelin-1 and blood pressure correlate with blunted constrictor responses and downregulation of endothelin(A), but not endothelin(B), receptors in an animal model of hypertension.” Clin Sci (Lond) 103 Suppl 48:357S-362S Details

    2001

    Davenport AP, Maguire JJ (2001), “The endothelin system in human saphenous vein graft disease.” Curr Opin Pharmacol 1(2):176-82 Details

    Katugampola SD, Maguire JJ, Matthewson SR, Davenport AP (2001), “[(125)I]-(Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man.” Br J Pharmacol 132(6):1255-60 Details

    Maguire JJ, Kuc RE, Davenport AP (2001), “Vasoconstrictor activity of novel endothelin peptide, ET-1(1 - 31), in human mammary and coronary arteries in vitro.” Br J Pharmacol 134(6):1360-6 Details

    2000

    Davenport AP, Maguire JJ (2000), “Urotensin II: fish neuropeptide catches orphan receptor.” Trends Pharmacol Sci 21(3):80-2 Details

    Maguire JJ, Davenport AP (2000), “No alteration in vasoconstrictor endothelin-B-receptor density or function in human coronary artery disease.” J Cardiovasc Pharmacol 36(5 Suppl 1):S380-1 Details

    Maguire JJ, Kuc RE, Davenport AP (2000), “Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1.” Br J Pharmacol 131(3):441-6 Details

    1999

    Maguire JJ, Davenport AP (1999), “The therapeutic potential of PD156707 and related butenolide endothelin antagonists.” Expert Opin Investig Drugs 8(1):71-8 Details

    Maguire JJ, Davenport AP (1999), “Endothelin receptor expression and pharmacology in human saphenous vein graft.” Br J Pharmacol 126(2):443-50 Details

    1998

    Maguire JJ, Davenport AP (1998), “Increased response to big endothelin-1 in atherosclerotic human coronary artery: functional evidence for up-regulation of endothelin-converting enzyme activity in disease.” Br J Pharmacol 125(2):238-40 Details

    Maguire JJ, Davenport AP (1998), “PD156707: a potent antagonist of endothelin-1 in human diseased coronary arteries and vein grafts.” J Cardiovasc Pharmacol 31 Suppl 1:S239-40 Details

    1997

    Maguire JJ, Johnson CM, Mockridge JW, Davenport AP (1997), “Endothelin converting enzyme (ECE) activity in human vascular smooth muscle.” Br J Pharmacol 122(8):1647-54 Details

    Maguire JJ, Kuc RE, Davenport AP (1997), “Affinity and selectivity of PD156707, a novel nonpeptide endothelin antagonist, for human ET(A) and ET(B) receptors.” J Pharmacol Exp Ther 280(2):1102-8 Details

    1996

    Maguire JJ, Kuc RE, Rous BA, Davenport AP (1996), “Failure of BQ123, a more potent antagonist of sarafotoxin 6b than of endothelin-1, to distinguish between these agonists in binding experiments.” Br J Pharmacol 118(2):335-42 Details

    1995

    Davenport AP, Kuc RE, Maguire JJ, Harland SP (1995), “ETA receptors predominate in the human vasculature and mediate constriction.” J Cardiovasc Pharmacol 26 Suppl 3:S265-7 Details

    Maguire JJ, Davenport AP (1995), “ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.” Br J Pharmacol 115(1):191-7 Details

    Maguire JJ, Kuc RE, Doherty AM, Davenport AP (1995), “Potency of PD155080, an orally active ETA receptor antagonist, determined for human endothelin receptors.” J Cardiovasc Pharmacol 26 Suppl 3:S362-4 Details

    1994

    Davenport AP, Kuc RE, Fitzgerald F, Maguire JJ, Berryman K, Doherty AM (1994), “[125I]-PD151242: a selective radioligand for human ETA receptors.” Br J Pharmacol 111(1):4-6 Details

    Davenport AP, Maguire JJ (1994), “Is endothelin-induced vasoconstriction mediated only by ETA receptors in humans?” Trends Pharmacol Sci 15(1):9-11 Details

    Maguire JJ, Bacon CR, Fujimoto M, Davenport AP (1994), “Myricerone caffeoyl ester (50-235) is a non-peptide antagonist selective for human ETA receptors.” J Hypertens 12(6):675-80 Details

    Maguire JJ, Kuc RE, O'Reilly G, Davenport AP (1994), “Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro.” Br J Pharmacol 113(1):49-54 Details

    1993

    Davenport AP, O'Reilly G, Molenaar P, Maguire JJ, Kuc RE, Sharkey A, Bacon CR, Ferro A (1993), “Human endothelin receptors characterized using reverse transcriptase-polymerase chain reaction, in situ hybridization, and subtype-selective ligands BQ123 and BQ3020: evidence for expression of ETB receptors in human vascular smooth muscle.” J Cardiovasc Pharmacol 22 Suppl 8:S22-5 Details