Themed Issues

Stay up-to-date with our must read themed articles by visiting our Published Issues and Sections page.

Increase the impact of your paper or review by submitting to a themed issue or section, see below for a list of our planned issues and sections.

Upcoming themed issues and sections

THEMED SECTION

G-protein coupled receptors

Guest Editor: Roger Summers

G-protein coupled receptors represent the largest group of targets utilised in therapeutics (~30% of drugs). Current drugs have been derived from knowledge of < 200 GPCRs of a family comprising ~ 1000 proteins. A major factor in the high attrition rate in development of new therapeutics based on GPCRs is a lack of fundamental understanding of key facets of GPCR biology, in particular, those governing the structural basis for ligand binding and activation, allosteric modulation of receptors by drugs acting at sites distinct from the natural ligand binding site and ligand - directed signalling (functional selectivity) and regulation of receptors. The recent meeting held in Sydney, Australia, on the Molecular Pharmacology of G Protein-Coupled Receptors highlighted major advances in our understanding of the three-dimensional structure of prototypical GPCRs and how structures and function change under the influence of ligands. Most current drugs acting at GPCRs have been developed based on targeting the endogenous agonist (orthosteric) binding site, but emerging evidence for the presence of allosteric sites on many GPCRs, which modulate receptor activity, gives great promise for the development of novel drugs with greater selectivity. Recent evidence for the concept of ligand-directed signalling is also challenging current theories of receptor-occupancy theory, which held that rank orders of efficacy were similar for all responses evoked by a given stimulus. It is now becoming clear that different ligands can have different efficacies at different signalling pathways, and that drugs acting as antagonists for one pathway can be full agonists for another. This provides the basis for the development of rational design of drugs that display unique signalling profiles at particular GPCRs and have improved therapeutic activity.

THEMED SECTION

Imaging in Pharmacology

Guest Editors: Anthony Davenport and Craig Daly

Imaging has become an important tool in virtually every branch of life science. Developments in imaging receptors both in vitro and in vivo are rapidly progressing with enhancements to both hardware and software which in turn leads to important new methodologies and applications. The British Journal of Pharmacology invites original manuscripts and reviews that will be considered under the standard review procedure for this Themed Section on Imaging in Pharmacology to include in vitro receptor interactions using fluorescence including receptor dimerization and down stream signalling, preclinical imaging of receptors in vivo using PET, MRI, combined PET/MRI and optical imaging.
 

THEMED SECTION

Receptor pharmacology methods under the spotlight
Papers due 31 August 2009

Guest Editor: Steven Charlton
Submit your original research here

G protein-coupled (or 7TM) receptors remain the most utilised class of protein targets in drug therapy. For decades the characteristics of new receptor ligands have been assessed using either binding techniques or measuring intracellular second messenger levels. Now, hundreds of new receptor ligands are made each day across the pharmaceutical industry and academia, necessitating the utilisation of higher-throughput methodologies. During the gradual process of converting test-tube experiments to plate-based assays, systems have been miniaturised and new detection technology has been invented. This industrialisation of pharmacology has resulted in a subtle shift in priority from high assay fidelity to the high reproducibility considered essential for routinely run experiments. So, rather than focus on generating assay systems that closely represent the physiological situation, assay developers have tended towards optimising primarily on window size, choosing the conditions that give the highest Z-factor.

This themed issue will be devoted to taking a closer look at how assay design can influence observed affinity and efficacy of receptor ligands, and how this can sometimes result in large differences in parameters that are often considered constant e.g. the equilibrium dissociation constant KA. It will also address common assay artifacts that often lead to the misinterpretation of data. To provide a balanced opinion, each review will be authored by an academic and industrial expert in the field. In addition, we invite the submission of novel work in the area of receptor pharmacology methods to be published in this themed issue, with the ultimate aim of redressing the balance between assay fidelity and throughput.
 

THEMED ISSUE

Cannabinoids: An update
Papers due 31 October 2009

Guest Editor: Steve Alexander
Submit your original research here

Although the cannabis plant has been exploited by man for millenia, modern scientific research into the cannabinoids came about with the description of delta9-tetrahydrocannabinol (THC) as the major psychoactive element of plant-derived preparations. A further milestone was the identification of synthetic cannabinoids which allowed definition of a specific cannabinoid receptor in brain tissues. The cloning of the CB1 cannabinoid receptor in the early 1990s and its identification as one of the most abundantly expressed 7-transmembrane receptors in the CNS underlined the importance of the cannabinoid system and led to the clarification of endogenous cannabinoid agents. These fatty acid derivatives, focused on the arachidonic acid derivatives anandamide and 2-arachidonoylglycerol, have been suggested to be distinct from traditional neurotransmitters, in that they appear not to be stored in vesicles, but rather to be made 'on demand' targeted directly at the sites of action. The current version of the endocannabinoid system includes multiple selective enzymatic pathways for endocannabinoid synthesis and transformation, as well as additional targets including the 7-transmembrane receptors, CB2 (primarily associated with the immune system) and GPR55 (although the grouping of this orphan receptor with the cannabinoid system is still contentious). Further targets of endocannabinoids and related molecules include the transmitter-gated channel, TRPV1 (the vanilloid receptor) and nuclear receptors (PPARalpha and gamma).
A major stimulus for pharmacological research was the development of selective antagonists for CB1 and CB2 receptors. Of these, rimonabant was available for a short time in Europe, under the trade name Acomplia, as a treatment for clinical obesity. Interest in the plant-derived cannabinoids has also seen a resurgence, with their exploitation in the treatment of multiple sclerosis, as well as an appetite stimulus for terminal cancer and AIDS patients. As with many other 7TM receptor systems, allosteric enhancers of CB1 receptor function may prove to be a further means of exploiting the endogenous system.
The expression of the endocannabinoid system in every organ where studies have taken place means that it provides something for everybody: molecular biologist or medicinal chemist; neuroscientist or nutritionist; osteologist or ophthalmologist; cardiovascular pharmacologist or reproduction biologist or toxicologist and more still... As such, therefore, the endocannabinoid system does stretch 'from bench to bedside'.

To see our previous themed issue on CB2 receptors click here

To see our previous themed issue on Cannabinoid Pharmacology click here 
 

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