British Journal of Pharmacology - Volume 165 Issue 4 (February 2012)

1. Presenting data: can you follow a recipe?

Date: Jan 25, 2012, Pages: 777-781

2. Statistical perspectives: all together NOT

Date: Jan 25, 2012, Pages: 782-784

3. Reply from Gordon B. Drummond and Brian D. M. Tom

Date: Jan 25, 2012, Pages: 785-786

4. The thermo‐TRP ion channel family: properties and therapeutic implications

Date: Jan 25, 2012, Pages: 787-801

The thermo‐transient receptor potentials (TRPs), a recently discovered family of ion channels activated by temperature, are expressed in primary sensory nerve terminals where they provide information about thermal changes in the environment. Six thermo‐TRPs have been characterised to date: TRP vanilloid (TRPV) 1 and 2 are activated by painful levels of heat, TRPV3 and 4 respond to non‐painful warmth, TRP melastatin 8 is activated by...

5. Inhibitory kappa B kinases as targets for pharmacological regulation

Date: Jan 25, 2012, Pages: 802-819

The inhibitory kappa B kinases (IKKs) are well recognized as key regulators of the nuclear factor kappa B (NF‐κB) cascade and as such represent a point of convergence for many extracellular agents that activate this pathway. The IKKs generally serve to transduce pro‐inflammatory and growth stimulating signals that contribute to major cellular processes but also play a key role in the pathogenesis of a number of human diseases. Therefore,...

6. Disruption of inflammatory signals by cytokine‐targeted therapies for inflammatory bowel diseases

Date: Jan 25, 2012, Pages: 820-828

Gut inflammation occurring in patients with inflammatory bowel diseases (IBD) is associated with an excessive immune response that is directed against constituents of the normal bacterial flora and results in the production of large amounts of inflammatory cytokines. Anti‐cytokine compounds, such as the neutralizing TNF antibodies, have been employed with clinical success in patients with IBD. However, nearly half of IBD patients are...

7. Insights into the pharmacological relevance of lysophospholipid receptors

Date: Jan 25, 2012, Pages: 829-844

The discovery of lysophospholipid (LP) 7‐transmembrane, G protein‐coupled receptors (GPCRs) that began in the 1990s, together with research into the functional roles of the major LPs known as lysophosphatidic acid (LPA) and sphingosine 1‐phosphate (S1P), have opened new research avenues into their biological processes and mechanisms. Major examples of LP signalling effects include embryogenesis, nervous system development, vascular...

8. Enhancing the utility of existing antibiotics by targeting bacterial behaviour?

Date: Jan 25, 2012, Pages: 845-857

The discovery of novel classes of antibiotics has slowed dramatically. This has occurred during a time when the appearance of resistant strains of bacteria has shown a substantial increase. Concern is therefore mounting over our ability to continue to treat infections in an effective manner using the antibiotics that are currently available. While ongoing efforts to discover new antibiotics are important, these must be coupled with...

9. Targeting synaptic pathology in multiple sclerosis: fingolimod to the rescue?

Date: Jan 25, 2012, Pages: 858-860

Multiple sclerosis (MS) is an inflammatory disorder affecting the brain and spinal cord. Major hallmarks of MS typically include inflammation, demyelination and axon degeneration, although recent studies have also implicated synaptic dysfunction and degeneration in disease pathogenesis. The discovery that treatment with the orally active immunomodulatory drug fingolimod (FTY720) confers benefits in animal models and human patients has...

10. Oral fingolimod rescues the functional deficits of synapses in experimental autoimmune encephalomyelitis

Date: Jan 25, 2012, Pages: 861-869

BACKGROUND AND PURPOSE Alterations of glutamate‐mediated synaptic transmission occur early during neuroinflammatory insults, and lead to degenerative neuronal damage in multiple sclerosis (MS) and also in experimental autoimmune encephalomyelitis (EAE), which is a murine model of MS. Fingolimod is an effective orally active agent for the treatment of MS, affecting lymphocyte invasion of the brain. However, it is still unclear if...

11. Br‐DIF‐1 accelerates dimethyl sulphoxide‐induced differentiation of P19CL6 embryonic carcinoma cells into cardiomyocytes

Date: Jan 25, 2012, Pages: 870-879

BACKGROUND AND PURPOSE Stem cell transplantation therapy is a promising option for treatment of severe ischaemic heart disease. Dimethyl sulphoxide (DMSO) differentiates P19CL6 embryonic carcinoma cells into cardiomyocyte‐like cells, but with low differentiation capacity. To improve the degree of this differentiation, we have assessed several derivatives of the differentiation‐inducing factor‐1 (DIF‐1), originally found in the cellular...

12. 2′‐Methoxy‐6‐methylflavone: a novel anxiolytic and sedative with subtype selective activating and modulating actions at GABA _A receptors

Date: Jan 25, 2012, Pages: 880-896

BACKGROUND AND PURPOSE Flavonoids are known to have anxiolytic and sedative effects mediated via actions on ionotropic GABA receptors. We sought to investigate this further. EXPERIMENTAL APPROACH We evaluated the effects of 2′‐methoxy‐6‐methylflavone (2′MeO6MF) on native GABAA receptors in new‐born rat hippocampal neurons and determined specificity from 18 human recombinant GABAA receptor subtypes expressed in Xenopus oocytes. We...

13. Stress‐induced anhedonia is associated with an increase in Alzheimer's disease‐related markers

Date: Jan 25, 2012, Pages: 897-907

BACKGROUND AND PURPOSE Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD‐related markers. EXPERIMENTAL APPROACH Anhedonia induced by a chronic mild stress (CMS) procedure, applied for 6 weeks, was used to select rats vulnerable or resistant ...

14. Pharmacological characterization of native α7 nicotinic ACh receptors and their contribution to depolarization‐elicited exocytosis in human chromaffin cells

Date: Jan 25, 2012, Pages: 908-921

BACKGROUND AND PURPOSE Expression of α7 nicotinic acetylcholine receptors (nAChRs) and their role in exocytosis have not yet been examined in human chromaffin cells. EXPERIMENTAL APPROACH To characterize these receptors and investigate their function, patch‐clamp experiments were performed in human chromaffin cells from organ donors. KEY RESULTS The nicotinic current provoked by 300 µM...

15. Molecular and functional characterization of the human platelet Na ⁺ /Ca ²⁺ exchangers

Date: Jan 25, 2012, Pages: 922-936

BACKGROUND AND PURPOSE The Na+/Ca2+ exchanger is a bi‐directional transporter that plays an important role in maintaining the concentration of cytosolic Ca2+ ([Ca2+]i) of quiescent platelets and increasing it during activation with some, but not all, agonists. There are two classes of Na+/Ca2+ exchangers: K+‐independent Na+/Ca2+ exchanger (NCX) and K+‐dependent Na+/Ca2+ exchanger (NCKX). Platelets have previously been shown to express NCKX1. However, initial studies from...