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

1. Pro‐oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes

Date: Jan 26, 2012, Pages: 1017-1033

BACKGROUND AND PURPOSE 3,4‐Methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5‐HT by monoamine oxidase (MAO), as well as the hepatic biotransformation of MDMA into pro‐oxidant reactive metabolites is thought to contribute...

2. Antiparkinsonian potential of targeting group III metabotropic glutamate receptor subtypes in the rodent substantia nigra pars reticulata

Date: Jan 26, 2012, Pages: 1034-1045

BACKGROUND AND PURPOSE Increased firing of the glutamatergic pathway between the subthalamic nucleus and substantia nigra pars reticulata (SNpr) contributes to the abnormal firing of motor circuits and subsequent motor deficits seen in Parkinson's disease. Broad spectrum agonist‐induced activation of presynaptic group III metabotropic glutamate (mGlu) receptors within the SNpr reduced glutamate release and...

3. Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain‐derived neurotrophic factor, β‐catenin and antidepressant‐like effects

Date: Jan 26, 2012, Pages: 1046-1057

BACKGROUND AND PURPOSE 5‐HT2A receptor antagonists improve antidepressant responses when added to 5‐HT‐selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5‐hydroxytryptaminergic system in the antidepressant‐like effect of this combined treatment, given subchronically. EXPERIMENTAL...

4. Nitroxide derivatives of non‐steroidal anti‐inflammatory drugs exert anti‐inflammatory and superoxide dismutase scavenging properties in A459 cells

Date: Jan 26, 2012, Pages: 1058-1067

BACKGROUND AND PURPOSE Inflammation and reactive oxygen species are associated with the promotion of various cancers. The use of non‐steroidal anti‐inflammatory drugs (NSAIDs) in cancer prevention treatments has been promising in numerous cancers. We report the evaluation of NSAIDs chemically modified by the addition of a redox‐active nitroxide group. TEMPO‐aspirin (TEMPO‐ASA) and TEMPO‐indomethacin (TEMPO‐IND) ...

5. The effect of K201 on isolated working rabbit heart mechanical function during pharmacologically induced Ca ²⁺ overload

Date: Jan 26, 2012, Pages: 1068-1083

BACKGROUND AND PURPOSE Reduced cardiac contractility has been associated with disrupted myocardial Ca2+ signalling. The 1,4 benzothiazepine K201 (JTV‐519) acts on several Ca2+ handling proteins and improves cardiac contractility in vivo in a variety of animal models of myocardial dysfunction. However, it is unclear whether this improvement depends on the systemic effects of K201 or if K201 reverses the effects of Ca2+ dysregulation,...

6. Plumbagin inhibits tumour angiogenesis and tumour growth through the Ras signalling pathway following activation of the VEGF receptor‐2

Date: Jan 26, 2012, Pages: 1084-1096

BACKGROUND AND PURPOSE Angiogenesis‐based therapy is an effective anti‐tumour strategy and previous reports have shown some beneficial effects of a naturally occurring bioactive compound plumbagin (5‐hydroxy‐2‐methyl‐1, 4‐naphthoquinone). Here, we sought to determine the biological effects of plumbagin on signalling mechanisms during tumour angiogenesis. EXPERIMENTAL APPROACH ...

7. Novel opioid cyclic tetrapeptides: Trp isomers of CJ‐15,208 exhibit distinct opioid receptor agonism and short‐acting κ opioid receptor antagonism

Date: Jan 26, 2012, Pages: 1097-1108

BACKGROUND AND PURPOSE The κ opioid receptor antagonists demonstrate potential for maintaining abstinence from psychostimulant abuse, but existing non‐peptide κ‐receptor selective antagonists show exceptionally long activity. We hypothesized that the L‐ and D‐Trp isomers of CJ‐15,208, a natural cyclic tetrapeptide reported to be a κ‐receptor antagonist in vitro, would demonstrate short‐acting, dose‐dependent antagonism in...

8. OX ₁ orexin/hypocretin receptor activation of phospholipase D

Date: Jan 26, 2012, Pages: 1109-1123

BACKGROUND AND PURPOSE Orexin receptors potently signal to lipid messenger systems, and our previous studies have suggested that PLD would be one of these. We thus wanted to verify this by direct measurements and clarify the molecular mechanism of the coupling. EXPERIMENTAL APPROACH Orexin receptor‐mediated PLD activation was investigated in CHO cells stably expressing...

9. Anti‐inflammatory effects of selective glucocorticoid receptor modulators are partially dependent on up‐regulation of dual specificity phosphatase 1

Date: Jan 26, 2012, Pages: 1124-1136

BACKGROUND AND PURPOSE It is thought that the anti‐inflammatory effects of glucocorticoids (GCs) are largely due to GC receptor (GR)‐mediated transrepression of NF‐κB and other transcription factors, whereas side effects are caused by activation of gene expression (transactivation). Selective GR modulators (SGRMs) that preferentially promote transrepression should retain anti‐inflammatory properties whilst ...

10. cAMP signalling protects proximal tubular epithelial cells from cisplatin‐induced apoptosis via activation of Epac

Date: Jan 26, 2012, Pages: 1137-1150

BACKGROUND AND PURPOSE Nephrotoxicity is the principal dose‐limiting factor for cisplatin chemotherapy and is primarily associated with proximal tubular epithelial cells, including disruption of cell adhesions and induction of apoptosis. Cell adhesion and survival is regulated by, amongst other factors, the small GTPase Rap and its activator, the exchange protein directly activated by cAMP (Epac). Epac is...

11. Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of gadodiamide

Date: Jan 26, 2012, Pages: 1151-1162

BACKGROUND AND PURPOSE Hyperphosphataemia is common in patients with nephrogenic systemic fibrosis (NSF). NSF has been linked to administration of gadolinium (Gd) chelates (GCs) and elevated serum phosphate levels accelerate the release of Gd from linear, non‐ionic GCs but not macrocyclic GCs. Hence, we determined whether hyperphosphataemia is a cofactor or risk factor for NSF by investigating the role of...

12. Silencing of P2Y ₂ receptors reduces intraocular pressure in New Zealand rabbits

Date: Jan 26, 2012, Pages: 1163-1172

BACKGROUND AND PURPOSE P2 receptors are involved in the regulation of ocular physiological processes like intraocular pressure (IOP). In the present study, the involvement of P2Y2 receptors in the hypertensive effect of nucleotides was investigated by use of antagonists and of a siRNA designed for the P2Y2 receptor. EXPERIMENTAL APPROACH Agonists of the...

13. Azelnidipine is a calcium blocker that attenuates liver fibrosis and may increase antioxidant defence

Date: Jan 26, 2012, Pages: 1173-1187

BACKGROUND AND PURPOSE Oxidative stress plays a critical role in liver fibrogenesis. Reactive oxygen species (ROS) stimulate hepatic stellate cells (HSCs), and ROS‐mediated increases in calcium influx further increase ROS production. Azelnidipine is a calcium blocker that has been shown to have antioxidant effects in endothelial cells and cardiomyocytes. Therefore, we evaluated the anti‐fibrotic and...

14. Acute alcohol intoxication reduces mortality, inflammatory responses and hepatic injury after haemorrhage and resuscitation in vivo

Date: Jan 26, 2012, Pages: 1188-1199

BACKGROUND AND PURPOSE Haemorrhagic shock and resuscitation (H/R) induces hepatic injury, strong inflammatory changes and death. Alcohol intoxication is assumed to worsen pathophysiological derangements after H/R. Here, we studied the effects of acute alcohol intoxication on survival, liver injury and inflammation after H/R, in rats. EXPERIMENTAL APPROACH ...

15. Reviewers for 2011

Date: Jan 26, 2012, Pages: 1200-1216