British Journal of Pharmacology 

About: British Journal of Pharmacology is an academic journal published by Wiley-Blackwell. The journal publishes majorly in the area(s): Receptor & Agonist. It has an ISSN identifier of 0007-1188. Over the lifetime, 24781 publications have been published receiving 1128830 citations. The journal is also known as: Br J Pharmacol & Br. J. Pharmacol..

Animal research: reporting in vivo experiments: the ARRIVE guidelines

Abstract: The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al (2010) ​ Table

Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?

Abstract: Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause. This article first reviews what is meant by the terms free radical, RS, antioxidant, oxidative damage and oxidative stress. It then critically examines methods used to trap RS, including spin trapping and aromatic hydroxylation, with a particular emphasis on those methods applicable to human studies. Methods used to measure oxidative damage to DNA, lipids and proteins and methods used to detect RS in cell culture, especially the various fluorescent ‘probes' of RS, are also critically reviewed. The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results. Keywords: Cell culture, free radical, reactive species, antioxidant, oxidative stress, oxidative damage, fluorescent probe, lipid peroxidation, superoxide Introduction Free radicals and other ‘reactive oxygen (ROS)/nitrogen/chlorine species' (for an explanation of these terms see Table 1) are widely believed to contribute to the development of several age-related diseases, and perhaps, even to the aging process itself (Halliwell & Gutteridge, 1999; Sohal et al., 2002) by causing ‘oxidative stress' and ‘oxidative damage' (terms explained in Table 2). For example, many studies have shown increased oxidative damage to all the major classes of biomolecules in the brains of Alzheimer's patients (Halliwell, 2001; Butterfield, 2002; Liu et al., 2003). Other diseases in which oxidative damage has been implicated include cancer, atherosclerosis, other neurodegenerative diseases and diabetes (Hagen et al., 1994; Chowienczyk et al., 2000; Halliwell, 2000a, 2001, 2002a, 2002b; Parthasarathy et al., 2000). If oxidative damage contributes significantly to disease pathology (Table 3 lists the criteria needed to establish this), then actions that decrease it should be therapeutically beneficial (Halliwell, 2001; Lee et al., 2002a; Liu et al., 2003). If the oxidative damage is involved in the origin of a disease, then successful antioxidant treatment should delay or prevent the onset of that disease (Halliwell, 1991, 2002a, 2002b; Galli et al., 2002; Steinberg & Witztum, 2002). To establish the role of oxidative damage (Table 3), it is therefore essential to be able to measure it accurately. For example, the failure of interventions with antioxidants such as vitamin E, β-carotene or ascorbate to decrease disease incidence in several human intervention trials may have simply been due to the failure of these compounds to decrease oxidative damage in the subjects tested (Halliwell, 1999a, 2000c; Levine et al., 2001; Meagher et al., 2001). In this review, we will examine the methods available to measure reactive species (RS) and oxidative damage, with a particular emphasis on those applicable to human studies. Table 1 Nomenclature of reactive species Table 2 Some key definitions Table 3 Criteria for implicating RS as a significant mechanism of tissue injury in human disease Measuring RS in vivo: basic principles Some fascinating techniques such as L-band electron spin resonance (ESR) with nitroxyl probes and magnetic resonance imaging spin trapping are under development to measure RS directly in whole animals (e.g. Berliner et al., 2001; Han et al., 2001; Utsumi & Yamada, 2003), but no probes are currently suitable for human use. Most RS persist for only a short time in vivo and cannot be measured directly. There are a few exceptions: examples include H2O2 (discussed below), and perhaps, NO•, in the sense that serum levels of NO2− have been claimed to measure vascular endothelial NO• synthesis (Kelm et al., 1999), despite the fact that NO2− is quickly oxidized to NO3− in vivo (Kelm et al., 1999; Oldreive & Rice-Evans, 2001). Essentially, there are two approaches to detecting transient RS: attempting to trap these species and measure the levels of the trapped molecules and measuring the levels of the damage done by RS, that is, the amount of oxidative damage. Sometimes other approaches are used. They include measurements of erythrocyte antioxidant defences and of total antioxidant activity of body fluids; falls in these parameters are often taken as evidence of oxidative stress. Erythrocytes cannot synthesize proteins, however, and their antioxidant enzyme levels may drop as they ‘age' in the circulation (Denton et al., 1975). Thus changes in their levels are more likely to reflect changes in the rates of red blood cell turnover: if this slows down, the circulating erythrocytes will be older on average and so levels of antioxidant enzymes in them will appear to fall. Vice versa, if an intervention accelerates red cell removal or increases erythropoiesis, levels of antioxidants in red cells will seem to rise. Hence, such data should be interpreted with caution. Depending on the method that is used to measure it, the plasma or serum ‘total antioxidant capacity' (TAC) usually involves major contributions from urate, ascorbate and sometimes albumin −SH groups (Benzie & Strain, 1996; Halliwell & Gutteridge, 1999; Prior & Cao, 1999; Rice-Evans, 2000; Bartosz, 2003), although different methods measure different things (Schlesier et al., 2002; Bartosz, 2003). Thus, for example, if plasma albumin levels fall, TAC will fall. If urate levels rise, TAC will rise. The multiple changes in blood chemistry that occur in sick people mean that TAC changes should be interpreted with caution. TAC is also influenced by diet, often because consumption of certain foods may produce changes in plasma ascorbate and/or urate levels (Halliwell, 2003b).

Guide to Receptors and Channels (GRAC), 3rd edition.

Abstract: The Fifth Edition of the 'Guide to Receptors and Channels' is a compilation of the major pharmacological targets divided into seven sections: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside suggestions for further reading. Available alongside this publication is a portal at http://www.GuideToPharmacology.org which is produced in close association with NC-IUPHAR and allows free online access to the information presented in the Fifth Edition.

Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo

Abstract: 1. Three analogues of L-arginine were characterized as inhibitors of endothelial nitric oxide (NO) synthase by measuring their effect on the endothelial NO synthase from porcine aortae, on the vascular tone of rings of rat aorta and on the blood pressure of the anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO) and NG-nitro-L-arginine methyl ester (L-NAME; all at 0.1-100 microM) caused concentration-dependent inhibition of the Ca2(+)-dependent endothelial NO synthase from porcine aortae. 3. L-NMMA, L-NIO and L-NAME caused an endothelium-dependent contraction and an inhibition of the endothelium-dependent relaxation induced by acetylcholine (ACh) in aortic rings. 4. L-NMMA, L-NIO and L-NAME (0.03-300 mg kg-1, i.v.) induced a dose-dependent increase in mean systemic arterial blood pressure accompanied by bradycardia. 5. L-NMMA, L-NIO and L-NAME (100 mg kg-1, i.v.) inhibited significantly the hypotensive responses to ACh and bradykinin. 6. The increase in blood pressure and bradycardia produced by these compounds were reversed by L-arginine (30-100 mg kg-1, i.v.) in a dose-dependent manner. 7. All of these effects were enantiomer specific. 8. These results indicate that L-NMMA, L-NIO and L-NAME are inhibitors of NO synthase in the vascular endothelium and confirm the important role of NO synthesis in the maintenance of vascular tone and blood pressure.

Some quantitative uses of drug antagonists. 1958.

Abstract: Various applications of pAx measurements are discussed based on the hypothesis that drugs and drug antagonists compete for receptors according to the mass law. Examples are given illustrating the use of pAx measurements to identify agonists which act on the same receptors and to compare the receptors of different tissues. Tests of competitive and noncompetitive antagonism are considered in relation to the antagonisms acetylcholine-atropine, histamine-atropine and acetylcholine-cinchonidine. A new measure, pAh, is introduced to express the activity of unsurmountable antagonists.