Roger Summers - Academia.edu (original) (raw)

Papers by Roger Summers

Research paper thumbnail of Atypical pharmacologies at β-adrenoceptors

British Journal of Pharmacology, Oct 1, 2008

Research paper thumbnail of β2-Adrenoceptor-mediated regulation of glucose uptake in skeletal muscle—ligand-directed signalling or a reflection of system complexity?

Naunyn-schmiedebergs Archives of Pharmacology, May 9, 2013

Research paper thumbnail of Recent progress in the understanding of relaxin family peptides and their receptors

British Journal of Pharmacology, Apr 26, 2017

Research paper thumbnail of Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane

British Journal of Pharmacology, Oct 1, 1969

Research paper thumbnail of Adrenoceptors in GtoPdb v.2023.1

IUPHAR/BPS Guide to Pharmacology CITE

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenocept... more The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [64, 194]. Adrenoceptors, α1 The three α1-adrenoceptor subtypes α1A, α1B and α1D are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. -(-)phenylephrine, methoxamine and cirazoline are agonists and prazosin and doxazosin antagonists considered selective for α1- relative to α2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy FLprazosin- QAPB) are used to examine cellular localisation of α1-adrenoceptors. α1-Adrenoceptor agonists are used as nasal decongestants; antagonists to treat symptoms of benign prostatic hyperplasia (alfuzosin, doxazosin, terazosin, tamsulosin and silodosin, with the last two compounds being α1A-adrenoceptor selective and claiming to relax bladder neck tone with less hypotension); and to ...

Research paper thumbnail of Inotropic responses to human gene 2 (B29) relaxin in a rat model of myocardial infarction (MI): effect of pertussis toxin

British Journal of Pharmacology, Nov 1, 2002

Research paper thumbnail of Relaxin-1–deficient mice develop an age-related progression of renal fibrosis

Kidney International, Jun 1, 2004

Research paper thumbnail of Increased Expression of the Relaxin Receptor (LGR7) in Human Endometrium during the Secretory Phase of the Menstrual Cycle

Annals of the New York Academy of Sciences, May 1, 2005

Research paper thumbnail of ‘Relaxin’ the stiffened heart and arteries: The therapeutic potential for relaxin in the treatment of cardiovascular disease

Pharmacology & Therapeutics, Nov 1, 2006

Research paper thumbnail of Enhanced serelaxin signalling in co-cultures of human primary endothelial and smooth muscle cells

British Journal of Pharmacology, Jan 15, 2016

Research paper thumbnail of ML290 is a biased allosteric agonist at the relaxin receptor RXFP1

Scientific Reports, Jun 7, 2017

Research paper thumbnail of Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors

Molecular Pharmacology, 2022

Research paper thumbnail of Deletion of GPR21 improves glucose homeostasis and inhibits the CCL2-CCR2 axis by divergent mechanisms

BMJ Open Diabetes Research & Care, 2021

IntroductionA potential role for the orphan G protein-coupled receptor, GPR21, in linking immune ... more IntroductionA potential role for the orphan G protein-coupled receptor, GPR21, in linking immune cell infiltration into tissues and obesity-induced insulin resistance has been proposed, although limited studies in mice are complicated by non-selective deletion of Gpr21.Research design and methodsWe hypothesized that a Gpr21-selective knockout mouse model, coupled with type 2 diabetes patient samples, would clarify these issues and enable clear assessment of GPR21 as a potential therapeutic target.ResultsHigh-fat feeding studies in Gpr21−/− mice revealed improved glucose tolerance and modest changes in inflammatory gene expression. Gpr21−/− monocytes and intraperitoneal macrophages had selectively impaired chemotactic responses to monocyte chemoattractant protein (MCP)-1, despite unaltered expression of Ccr2. Further genotypic analysis revealed that chemotactic impairment was due to dysregulated monocyte polarization. Patient samples revealed elevated GPR21 expression in peripheral b...

Research paper thumbnail of Relaxin family peptide receptors in GtoPdb v.2021.3

IUPHAR/BPS Guide to Pharmacology CITE, 2021

Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on R... more Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [18, 81]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1, relaxin, relaxin-3 (also known as INSL7), insulin-like peptide 3 (INSL3) and INSL5. Species homologues of relaxin have distinct pharmacology and relaxin interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [184]. relaxin-3 is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [183]. INSL5 is the ligand for RXFP4 but is a weak antagonist of RXFP3. relaxin and INSL3 have multiple complex binding interactions with RXFP1 [189] and RXFP2 [91] which direct the N-terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct re...

Research paper thumbnail of BRL37344 stimulates glucose uptake into skeletal muscle by β2-adrenoceptor mediated translocation of GLUT4 without causing receptor desensitization

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Research paper thumbnail of THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein‐coupled receptors

British Journal of Pharmacology, 2019

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. ... more The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein‐coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic rec...

Research paper thumbnail of Divergent effects of strontium and calcium‐sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity

British Journal of Pharmacology, 2018

Background and PurposeStrontium ranelate, a drug approved and until recently used for the treatme... more Background and PurposeStrontium ranelate, a drug approved and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium‐sensing (CaS) receptor. However, it is not known whether bone‐targeted CaS receptor positive allosteric modulators (PAMs; calcimimetics) represent an alternative (or adjunctive) therapy to strontium (Sr2+o).Experimental ApproachWe assessed three structurally distinct calcimimetics [cinacalcet, AC‐265347 and a benzothiazole tri‐substituted urea (BTU‐compound 13)], alone and in combination with extracellular calcium (Ca2+o) or Sr2+o, in G protein‐dependent signalling assays and trafficking experiments in HEK293 cells and their effects on cell differentiation, tartrate‐resistant acid phosphatase (TRAP) activity and hydroxyapatite resorption assays in human blood‐derived osteoclasts.Key ResultsSr2+o activated CaS receptor‐dependent signalling in HEK293 cells in a similar manner to Ca2+o, and inhibited the matur...

Research paper thumbnail of G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Pharmacological Reviews, 2017

Research paper thumbnail of Characterization of β1- and β2-adrenoceptors in rat skeletal muscles

Biochemical Pharmacology, Oct 1, 1991

Research paper thumbnail of Physiological or pathological — a role for relaxin in the cardiovascular system?

Current Opinion in Pharmacology, Apr 1, 2003

Research paper thumbnail of Atypical pharmacologies at β-adrenoceptors

British Journal of Pharmacology, Oct 1, 2008

Research paper thumbnail of β2-Adrenoceptor-mediated regulation of glucose uptake in skeletal muscle—ligand-directed signalling or a reflection of system complexity?

Naunyn-schmiedebergs Archives of Pharmacology, May 9, 2013

Research paper thumbnail of Recent progress in the understanding of relaxin family peptides and their receptors

British Journal of Pharmacology, Apr 26, 2017

Research paper thumbnail of Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane

British Journal of Pharmacology, Oct 1, 1969

Research paper thumbnail of Adrenoceptors in GtoPdb v.2023.1

IUPHAR/BPS Guide to Pharmacology CITE

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenocept... more The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [64, 194]. Adrenoceptors, α1 The three α1-adrenoceptor subtypes α1A, α1B and α1D are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. -(-)phenylephrine, methoxamine and cirazoline are agonists and prazosin and doxazosin antagonists considered selective for α1- relative to α2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy FLprazosin- QAPB) are used to examine cellular localisation of α1-adrenoceptors. α1-Adrenoceptor agonists are used as nasal decongestants; antagonists to treat symptoms of benign prostatic hyperplasia (alfuzosin, doxazosin, terazosin, tamsulosin and silodosin, with the last two compounds being α1A-adrenoceptor selective and claiming to relax bladder neck tone with less hypotension); and to ...

Research paper thumbnail of Inotropic responses to human gene 2 (B29) relaxin in a rat model of myocardial infarction (MI): effect of pertussis toxin

British Journal of Pharmacology, Nov 1, 2002

Research paper thumbnail of Relaxin-1–deficient mice develop an age-related progression of renal fibrosis

Kidney International, Jun 1, 2004

Research paper thumbnail of Increased Expression of the Relaxin Receptor (LGR7) in Human Endometrium during the Secretory Phase of the Menstrual Cycle

Annals of the New York Academy of Sciences, May 1, 2005

Research paper thumbnail of ‘Relaxin’ the stiffened heart and arteries: The therapeutic potential for relaxin in the treatment of cardiovascular disease

Pharmacology & Therapeutics, Nov 1, 2006

Research paper thumbnail of Enhanced serelaxin signalling in co-cultures of human primary endothelial and smooth muscle cells

British Journal of Pharmacology, Jan 15, 2016

Research paper thumbnail of ML290 is a biased allosteric agonist at the relaxin receptor RXFP1

Scientific Reports, Jun 7, 2017

Research paper thumbnail of Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors

Molecular Pharmacology, 2022

Research paper thumbnail of Deletion of GPR21 improves glucose homeostasis and inhibits the CCL2-CCR2 axis by divergent mechanisms

BMJ Open Diabetes Research & Care, 2021

IntroductionA potential role for the orphan G protein-coupled receptor, GPR21, in linking immune ... more IntroductionA potential role for the orphan G protein-coupled receptor, GPR21, in linking immune cell infiltration into tissues and obesity-induced insulin resistance has been proposed, although limited studies in mice are complicated by non-selective deletion of Gpr21.Research design and methodsWe hypothesized that a Gpr21-selective knockout mouse model, coupled with type 2 diabetes patient samples, would clarify these issues and enable clear assessment of GPR21 as a potential therapeutic target.ResultsHigh-fat feeding studies in Gpr21−/− mice revealed improved glucose tolerance and modest changes in inflammatory gene expression. Gpr21−/− monocytes and intraperitoneal macrophages had selectively impaired chemotactic responses to monocyte chemoattractant protein (MCP)-1, despite unaltered expression of Ccr2. Further genotypic analysis revealed that chemotactic impairment was due to dysregulated monocyte polarization. Patient samples revealed elevated GPR21 expression in peripheral b...

Research paper thumbnail of Relaxin family peptide receptors in GtoPdb v.2021.3

IUPHAR/BPS Guide to Pharmacology CITE, 2021

Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on R... more Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [18, 81]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1, relaxin, relaxin-3 (also known as INSL7), insulin-like peptide 3 (INSL3) and INSL5. Species homologues of relaxin have distinct pharmacology and relaxin interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [184]. relaxin-3 is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [183]. INSL5 is the ligand for RXFP4 but is a weak antagonist of RXFP3. relaxin and INSL3 have multiple complex binding interactions with RXFP1 [189] and RXFP2 [91] which direct the N-terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct re...

Research paper thumbnail of BRL37344 stimulates glucose uptake into skeletal muscle by β2-adrenoceptor mediated translocation of GLUT4 without causing receptor desensitization

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Research paper thumbnail of THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein‐coupled receptors

British Journal of Pharmacology, 2019

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. ... more The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein‐coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic rec...

Research paper thumbnail of Divergent effects of strontium and calcium‐sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity

British Journal of Pharmacology, 2018

Background and PurposeStrontium ranelate, a drug approved and until recently used for the treatme... more Background and PurposeStrontium ranelate, a drug approved and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium‐sensing (CaS) receptor. However, it is not known whether bone‐targeted CaS receptor positive allosteric modulators (PAMs; calcimimetics) represent an alternative (or adjunctive) therapy to strontium (Sr2+o).Experimental ApproachWe assessed three structurally distinct calcimimetics [cinacalcet, AC‐265347 and a benzothiazole tri‐substituted urea (BTU‐compound 13)], alone and in combination with extracellular calcium (Ca2+o) or Sr2+o, in G protein‐dependent signalling assays and trafficking experiments in HEK293 cells and their effects on cell differentiation, tartrate‐resistant acid phosphatase (TRAP) activity and hydroxyapatite resorption assays in human blood‐derived osteoclasts.Key ResultsSr2+o activated CaS receptor‐dependent signalling in HEK293 cells in a similar manner to Ca2+o, and inhibited the matur...

Research paper thumbnail of G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Pharmacological Reviews, 2017

Research paper thumbnail of Characterization of β1- and β2-adrenoceptors in rat skeletal muscles

Biochemical Pharmacology, Oct 1, 1991

Research paper thumbnail of Physiological or pathological — a role for relaxin in the cardiovascular system?

Current Opinion in Pharmacology, Apr 1, 2003