British Journal of Pharmacology
© The British Pharmacological Society
The cover picture has kindly been provided by Professor SPH Alexander (2008).
The image depicts a schematic representation of pharmacology, divided into drug sources and molecular & tissue targets.
Tissue targets include the brain, lungs, pancreas and blood vessels.
Molecular targets include receptors, ion channels, enzymes and DNA.
Drug sources include natural products and medicinal chemistry.
This cover picture has been modified from an image kindly provided by Dr KL Wright, Dr M Duncan and Dr KA Sharkey (Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation British Journal of Pharmacology advance online publication 1 October 2007; doi: 10.1038/sj.bjp.0707486)
The cover image is a graphical representation of the sites where cannabinoid (CB) receptors regulate neuroimmune interactions in the gastrointestinal tract. CB1 and CB2 receptors are expressed in the enteric nervous system and on immune cells in the normal gut. During inflammation, when bacteria can enter the gut there is enhanced expression of CB2 receptors on epithelial cells at ulcer margins. CB receptors are also expressed on primary afferent nerves that project to the spinal cord and regulate visceral sensation and pain.
The cover picture has kindly been provided by Dr CJ Daly, Dr M Shafaroudi & Professor JC McGrath (2006).
The image demonstrates the presence of a patchwork of both angiotensin receptors (yellow) and alpha-adrenoceptors (green) on endothelial cells of a young adult mouse aorta. A 3D view of the luminal surface of the opened artery is shown. The blue surface in the background shows the autofluorescence of the folded internal elastic lamina underlying the endothelium. The dark surface on the right is a 2D plane interposed to show a different view of receptors on endothelial cells projecting into the lumen. The image volume was collected using a laser scanning confocal microscope and the data was rendered with IMARIS imaging software. Yellow indicates the binding of TMR-AII to endothelial angiotensin receptors whilst green indicates binding of QAPB to alpha-adrenoceptors.
Images on the cover from left to right:
• Based on PDB structure of bovine rhodopsin: accession number 1F88. Reprinted with permission from (Palczewski, K. et al., Science 289, 739-745) copyright (2000) AAAS.
• Based on the PDB structure of the Kcsa potassium channel; accession number 1J95. Reproduced with permission from Macmillan Publishers Ltd: Nature (Zhou, M. et al., Nature 411, 657-661) copyright (2001)
• Based on the crystal structure of the HIV protease bound to the inhibitor amprenavir. Reproduced with permission from Nature Reviews Drug Discovery (Blundell, T. L. et al., Nature Rev., Drug Discov. 1, 45-54) copyright (2002) Macmillan Magazines Ltd.
This cover picture was kindly provided by Dr Anthony Ford. The image was taken from the review article 'Purinoceptors as therapeutic targets for lower urinary tract dysfunction' within the supplement. The artwork was provided by KO Studios courtesy of Rohce, Palo Alto, USA.
The image is a schematic diagram of the neural circuits controlling continence and micturition. The majority of A delta and C-afferents that innervate the urinary bladder and urethra are found in pelvic nerves, which also contain parasympathetic efferents originating from the sacral spinal cord. The remaining bladder afferents are carried by hypogastric nerves, which also contain sympathetic efferents originating from the thoracolumber spinal cord. Sacral somatic afferent and efferent innervation to the external urethral sphincter is via pudendal nerves. Under normal physiological condition in adults the micturition reflex is controlled predominantly by A delta afferents communicating via the spinal cord to supraspinal centers in the pons and cortex. Under pathophysiological conditions or with aging, spinal reflex mechanisms mediated by C-fibre afferents may become dominant.
Biographical notes on the BPS founders (Based on W F Bynum, 1981, Early History of the British Pharmacological Society, published by the BPS for its 50th anniversary):
H H Dale (1875-1968): A Nobel laureate (1936), and one of the giants of 20th century medical science. Dale trained in natural sciences in Cambridge before working with Bayliss and Starling in the Department of Physiology at University College London. Dale joined the Wellcome Research Laboratories in 1904, from which came a succession of classical studies of the pharmacology of a variety of endogenous mediators. Dale was one of the 3 founders of the British Pharmacological Society, and remained an influential and active figure in the Society for many years.
J A Gunn (1882-1958): Born in Orkney and trained in science and medicine in Edinburgh. Assistant to Sir Thomas Fraser in the Department of Materia Medica before moving to Oxford in 1912, where he was later appointed as the first Professor of Pharmacology. Gunn was the main instigator behind the radical revision of the British Pharmacopoeia which began in 1928. He was the driving force behind the foundation of the British Pharmacological Society, and the Oxford department hosted many of its early meetings.
W E Dixon (1871-1931): Trained in Medicine at St Thomas's Hospital, London, and was appointed Professor of Materia Medica at Kings College London before moving to Cambridge as a Reader in Pharmacology in 1909. He remained in Cambridge as an influential teacher and advocate of pharmacology in relation to medicine. He was greatly involved in founding the British Pharmacological Society, though he died prematurely just before its first scientific meeting.
This cover picture was kindly provided by Dr Dimitris Trafalis. The image is taken from the following research project: Geromichalos GD & Trafalis DTP (2005) Assault of estrogen receptors and estrogen-dependent neoplasms by lactam steroidal alkylators (supported by Balkan Union of Oncology).
The image is an insertion of an androsterone D-lactam steroidal alkylating ester, depicted in stick and coloured by atom type, into the hydrophobic cavity of the human estrogen alpha-receptor ligand binding domain (hERα-LBD). The ligand binding site is illustrated in mesh and coloured according to surrounding helices, which are depicted as cartoons and coloured by chain. Polar interaction with water53 molecule depicted as a hot pink sphere and located at the gap entrance of the ligand-binding cavity (depicted as broken line). The molecule was built in 3D coordinates and its best (lower energy) conformation was detected by geometrical optimization of its structure as implemented in the SPARTAN '04 molecular modeling program suite. Geometry optimization was accomplished via quantum-chemical calculations by utilizing the ab initio Hartree-Fock method with 3-21G basis set. Docking calculations were performed with GLUE program (part of the GRID-22 package). X-ray structure of hERα was obtained from the Brookhaven Protein Data Bank (PDB entry code: 1ERR). PyMOL was employed in order to visualize the molecules and the results of the docking.
This cover picture was kindly provided by Craig Daly and John Christie McGrath (Glasgow University, Scotland). The image is taken from the following article: Daly CJ & McGrath JC (2005) The use of fluorescent ligands and proteins to visualise adrenergic receptors. In: The Adrenergic Receptors in the 21st Century: The Receptor Series. Editor: Dianne M. Perez, Series Editor: Kim Neve. Humana Press, Inc.
The plate shows distribution of intracellular Alpha-1-adrenoceptors in human vascular smooth muscle cells. A fluorescent (BODIPY) form of prazosin (30 nM) binds to two isolated smooth muscle cells from a skeletal muscle resistance artery. Confocal image data was reconstructed using the iso-surface module of the 3D analysis software AMIRA (TGS). Different intensities of fluorescent ligand-binding are depicted as surfaces. The light blue transparent surface shows the lowest intensities at the plasmalemmal membrane. Intensities increase green/orange/yellow/red. In the high intensity red areas (intracellular endoplasmic vesicles) the meshwork generated by the software to create the surface is shown.
This cover picture was kindly provided by Craig Daily and John Christie McGrath (Glasgow University, Scotland).
The plate shows α1-adrenoceptors throughout the cell body of hepatocytes with no significant concentration on the cell surface. Binucleated hepatocytes in a mouse liver lobe are visualised by confocal microscopy and a 3D image is reconstructed using IMARIS software. Receptors are shown by the binding of a fluorescent form of an α1-adrenoceptor antagonist (BODIPY FL-prazosin, blue: excitation 488 nm, detection 515 nm) and nuclei by propidium iodide (pink: excitation 488 nm, detection 550 nm (Daly, C.J. & McGrath, J.C. (2003). Pharmacol. Ther. 100: 101-118; McGrath, J.C. et al. (1996). Trends Pharmacol. Sci. 17 (11): 393-399).
The cover picture was kindly provided by Marcelo Ortells and Georgina Barrantes (Buenos Aires, Argentina) and is Carbamazepine docked in the α4-β2 neuronal nicotinic receptor channel. (See Br. J. Pharmacol. (2002) 136, 883-895.)
This cover picture has kindly been provided by A Weston (Manchester) and is a cross-section of rat mesenteric artery, labelled for twin-pore domain potassium channels (red), with nuclei (blue) and internal lamina (green) shown.