Imperial College London

DrChristopherJohn

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Reader in Pharmacology
 
 
 
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Contact

 

+44 (0)20 3313 8039c.john

 
 
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Location

 

6N5cCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

27 results found

Ma Y, Ratnasabapathy R, De Backer I, Izzi-Engbeaya C, Nguyen-Tu M-S, Cuenco J, Jones B, John C, Lam B, Rutter G, Yeo G, Dhillo W, Gardiner Jet al., 2020, Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release, JCI insight, Vol: 5, ISSN: 2379-3708

Glucokinase (GK) is highly expressed in the hypothalamic paraventricular nucleus (PVN); however, its role is currently unknown. We found that GK in the PVN acts as part of a glucose-sensing mechanism within the PVN that regulates glucose homeostasis by controlling glucagon-like peptide 1 (GLP-1) release. GLP-1 is released from enteroendocrine L cells in response to oral glucose. Here we identify a brain mechanism critical to the release of GLP-1 in response to oral glucose. We show that increasing expression of GK or injection of glucose into the PVN increases GLP-1 release in response to oral glucose. On the contrary, decreasing expression of GK or injection of nonmetabolizable glucose into the PVN prevents GLP-1 release. Our results demonstrate that gluco-sensitive GK neurons in the PVN are critical to the response to oral glucose and subsequent release of GLP-1.

Journal article

Muttoni S, Ardissino M, John C, 2019, Classical psychedelics for the treatment of depression and anxiety: A systematic review, Journal of Affective Disorders, Vol: 258, Pages: 11-24, ISSN: 0165-0327

BackgroundDepression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these conditions, but their efficacy is limited. Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may be a promising alternative for patients unresponsive to traditional treatments. This review aims to determine the efficacy and tolerability of psychedelics in the management of resistant depression.MethodsClinical trials investigating psychedelics in patients with depression and/or anxiety were searched via MEDLINE, EMBASE and PsychINFO. Efficacy was assessed by measuring symptom improvement from baseline, and tolerability was evaluated by noting the incidence and type of adverse effects reported. Risk of bias was assessed.ResultsSeven studies, with 130 patients, were analysed in this review. Three were conducted in patients with depression, two in patients with anxiety and two in patients with both. In a supportive setting, ayahuasca, psilocybin, and LSD consistently produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Psychedelics were well-tolerated. The most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure.LimitationsAt present, the number of studies on this subject is very limited; and the number of participating patients within these is also limited as the treatment under investigations is a relatively novel concept.ConclusionsThough further evidence is required, psychedelics appear to be effective in significantly reducing symptoms of depression and anxiety and are well-tolerated.

Journal article

Basharat S, Parker JA, Murphy KG, Bloom SR, Buckingham JC, John CDet al., 2014, Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary- adrenal axis in rats, Journal of Endocrinology, Vol: 221, Pages: 229-234, ISSN: 0022-0795

Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis. We hypothesised that leptin would attenuate the HPA axis response to sepsis. We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1β secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.

Journal article

Mehet DK, Philip J, Solito E, Buckingham JC, John CDet al., 2012, Evidence From In Vitro and In Vivo Studies Showing that Nuclear Factor-Kappa B Within the Pituitary Folliculostellate Cells and Corticotrophs Regulates Adrenocorticotrophic Hormone Secretion in Experimental Endotoxaemia, JOURNAL OF NEUROENDOCRINOLOGY, Vol: 24, Pages: 862-873, ISSN: 0953-8194

Journal article

John CD, Gavins FNE, Buss NAPS, Cover PO, Buckingham JCet al., 2008, Annexin A1 and the formyl peptide receptor family: neuroendocrine and metabolic aspects, CURRENT OPINION IN PHARMACOLOGY, Vol: 8, Pages: 765-776, ISSN: 1471-4892

Journal article

John CD, Sahni V, Mehet D, Morris JF, Christian HC, Perretti M, Flower RJ, Solito E, Buckingham JCet al., 2007, Formyl peptide receptors and the regulation of ACTH secretion: targets for annexin A1, lipoxins, and bacterial peptides, FASEB JOURNAL, Vol: 21, Pages: 1037-1046, ISSN: 0892-6638

Journal article

John CD, Theogaraj E, Christian HC, Morris JF, Smith SF, Buckingham JCet al., 2006, Time-specific effects of perinatal glucocorticoid treatment on anterior pituitary morphology, annexin 1 expression and adrenocorticotrophic hormone secretion in the adult female rat, JOURNAL OF NEUROENDOCRINOLOGY, Vol: 18, Pages: 949-959, ISSN: 0953-8194

Journal article

Warne JP, John CD, Christian HC, Morris JF, Flower RJ, Sugden D, Solito E, Gillies GE, Buckingham JCet al., 2006, Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol: 291, Pages: E1264-E1273, ISSN: 0193-1849

Journal article

Theogaraj E, John CD, Dewar A, Buckingham JC, Smith SFet al., 2006, The long-term effects of perinatal glucocorticoid exposure on the host defence system of the respiratory tract, JOURNAL OF PATHOLOGY, Vol: 210, Pages: 85-93, ISSN: 0022-3417

Journal article

Buckingham JC, Sahni V, Morris JF, Christian HC, Solito E, John CDet al., 2006, Annexin 1 dependent actions of glucocorticoids in the anterior pituitary gland - role of the formyl peptide receptor family, 6th International Congress of Neuroendocrinology, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: 53-54, ISSN: 0091-3022

Conference paper

McArthur S, Siddique ZL, Christian HC, Capone G, Theogaraj E, John CD, Smith SF, Morris JF, Buckingham JC, Gillies GEet al., 2006, Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats, ENDOCRINOLOGY, Vol: 147, Pages: 1904-1915, ISSN: 0013-7227

Journal article

Rodrigues-Lisoni FC, Mehet DK, Peitl P, John CD, da Silva WA, Tajara E, Buckingham JC, Solito Eet al., 2006, In vitro and in vivo studies on CCR10 regulation by Annexin A1 (vol 580, pg 1431, 2006), FEBS LETTERS, Vol: 580, Pages: 1908-1908, ISSN: 1873-3468

Journal article

Rodrigues-Lisoni FC, Mehemet DK, Peitl P, John CD, Tajara E, Buckingham JC, Solito Eet al., 2006, In vitro and in vivo studies on CCR10 regulation by Annexin A1, FEBS LETTERS, Vol: 580, Pages: 1431-1438, ISSN: 0014-5793

Journal article

Buckingham JC, John CD, Solito E, Tierney T, Flower RJ, Christian H, Morris Jet al., 2006, Annexin 1, glucocorticoids, and the neuroendocrine-immune interface, NEUROENDOCRINE AND IMMUNE CROSSTALK, Vol: 1088, Pages: 396-409, ISSN: 0077-8923

Journal article

Theogaraj E, John CD, Christian HC, Morris JF, Smith SF, Buckingham JCet al., 2005, Perinatal glucocorticoid treatment produces molecular, functional, and morphological changes in the anterior pituitary gland of the adult male rat, ENDOCRINOLOGY, Vol: 146, Pages: 4804-4813, ISSN: 0013-7227

Journal article

John CD, Christian HC, Morris JF, Flower RJ, Solito E, Buckingham JCet al., 2004, Annexin 1 and the regulation of endocrine function, TRENDS IN ENDOCRINOLOGY AND METABOLISM, Vol: 15, Pages: 103-109, ISSN: 1043-2760

Journal article

John CD, Christian HC, Morris JF, Flower RJ, Solito E, Buckingham JCet al., 2003, Kinase-dependent regulation of the secretion of thyrotrophin and luteinizing hormone by glucocorticoids and annexin 1 peptides, JOURNAL OF NEUROENDOCRINOLOGY, Vol: 15, Pages: 946-957, ISSN: 0953-8194

Journal article

John CD, Buckingham JC, 2003, Cytokines: regulation of the hypothalamo-pituitary-adrenocorticaI axis, CURRENT OPINION IN PHARMACOLOGY, Vol: 3, Pages: 78-84, ISSN: 1471-4892

Journal article

Buckingham JC, Solito E, John CD, Tierney T, Taylor AD, Flower RJ, Christian HC, Morris JFet al., 2003, Annexin 1: A paracrine/juxtacrine mediator of glucocorticoid action in the neuroendocrine system, Cell Biochemistry and Function, Vol: 21, Pages: 217-221

Journal article

John C, Cover P, Solito E, Morris J, Christian H, Flower R, Buckingham Jet al., 2002, Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: Roles of the N-terminal domain and protein kinase C, ENDOCRINOLOGY, Vol: 143, Pages: 3060-3070, ISSN: 0013-7227

Journal article

Cover PO, Baanah-Jones F, John CD, Buckingham JCet al., 2002, Annexin 1 (lipocortin 1) mimics inhibitory effects of glucocorticoids on testosterone secretion and enhances effects of interleukin-1β, ENDOCRINE, Vol: 18, Pages: 33-39, ISSN: 0969-711X

Journal article

John CD, Theogaraj E, Dewar A, Smith SF, Buckingham JCet al., 2002, Effects of perinatal dexamethasone treatment on immune cell distribution in the adult rat., BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188

Journal article

Theogaraj E, John CD, Smith SF, Buckingham JCet al., 2002, The programming actions of glucocorticoids on ANXA-1 expression in the hypothalamic-pituitary adrenal axis of adult rats treated perinatally with dexamethasone, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188

Journal article

Philip JG, John CD, Cover PO, Morris JF, Christian HC, Flower RJ, Buckingham JCet al., 2001, Opposing influences of glucocorticoids and interleukin-1β on the secretion of growth hormone and ACTH in the rat <i>in vivo</i>:: role of hypothalamic annexin 1, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 134, Pages: 887-895, ISSN: 0007-1188

Journal article

John CD, Solito E, Mulla A, Morris JF, Flower RJ, Buckingham JCet al., 2001, Dexamethasone induces serine phosphorylation of annexin 1 in pituitary cells and suppresses ACTH release by a PKC-dependent mechanism., BRITISH JOURNAL OF PHARMACOLOGY, Vol: 133, Pages: U20-U20, ISSN: 0007-1188

Journal article

Taylor AD, Philip JG, John CD, Cover PO, Morris JF, Flower RJ, Buckingham JCet al., 2000, Annexin 1 (Lipocortin 1) mediates the glucocorticoid inhibition of cyclic adenosine 3′,5′-monophosphate-stimulated prolactin secretions, ENDOCRINOLOGY, Vol: 141, Pages: 2209-2219, ISSN: 0013-7227

Journal article

John CD, Cover PO, Taylor AD, Morris JF, Flower RJ, Solito E, Buckingham JCet al., 1999, Evidence from <i>in vivo</i> and <i>in vitro</i> studies that the inhibitory actions of lipocortin 1 on anterior pituitary function require amino acid residues 13-26, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 126, Pages: U74-U74, ISSN: 0007-1188

Journal article

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