Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti-MRSA fluoroquinolone JNJ-Q2.

abstract：:1 The beta-adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea-pig liver slices, in contrast to the large hyperpolarizations seen with alpha-agonists. However, after a selective alpha-adrenoceptor agonist has been applied, the response t...

journal_title：British journal of pharmacology

authors： Jenkinson DH,Koller K

更新日期：1977-01-01 00:00:00

abstract：:The concentration of intracellular free Ca2+ ( [Ca2+]i) in human blood platelets was measured by use of the fluorescent probe quin-2. 5-Hydroxytryptamine (5-HT) caused a rapid increase of [Ca2+]i in the presence or absence of Ca2+ in the medium. The [Ca2+]i-rise was less marked in the absence of Ca2+ and could be anta...

journal_title：British journal of pharmacology

authors： Erne P,Pletscher A

更新日期：1985-02-01 00:00:00

abstract：:1 Inactivation of prostaglandin E2 in the pulmonary circulation of rabbits in vivo was measured by comparing the hypotensive effects of doses given intravenously and intra-arterially. 2 Di-4-phloretin phosphate (DPP) 25-100 mug kg-1 min-1 inhibited the inactivation of prostaglandin E2 in the pulmonary circulation. 3 T...

journal_title：British journal of pharmacology

authors： Crutchley DJ,Piper PJ

更新日期：1975-07-01 00:00:00

abstract：:1. Voltage-operated calcium channel (VOCC) antagonists are effective antihypertensive and antianginal agents but they also depress myocardial contractility. 2. We compared four L-type calcium channel antagonists, felodipine, nifedipine, amlodipine and verapamil and a relatively T-type selective calcium channel antagon...

journal_title：British journal of pharmacology

authors： Sarsero D,Fujiwara T,Molenaar P,Angus JA

更新日期：1998-09-01 00:00:00

abstract：:1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (I...

journal_title：British journal of pharmacology

authors： Wang JP,Raung SL,Hsu MF,Chen CC

更新日期：1994-11-01 00:00:00

abstract：:Fresh human erythrocytes were washed and incubated at 37 degrees C in physiological saline buffered with Tris, containing calcium and either neuraminidase or trypsin or both enzymes together. Each enzyme alone, as well as both together, released similar amounts of sialic acids without haemolysis, apparently therefore ...

journal_title：British journal of pharmacology

authors： Born GV,Housley GM

更新日期：1983-06-01 00:00:00

abstract：:A new canine model of endotoxin shock has been developed in which spontaneous recovery of cardiovascular function is largely prevented, the haemodynamic effects of anaesthesia are minimized and intravascular volume replacement is given. This model has been evaluated using two groups of five adult mongrel dogs anaesthe...

journal_title：British journal of pharmacology

authors： Evans SF,Hinds CJ,Varley JG

更新日期：1984-10-01 00:00:00

abstract：:The metabolism and efficacy of 5-fluorouracil (FUra) and other fluorinated pyrimidine (FP) derivatives have been intensively investigated for over fifty years. FUra and its antimetabolites can be incorporated at RNA- and DNA-levels, with RNA level incorporation provoking toxic responses in human normal tissue, and DNA...

journal_title：British journal of pharmacology

authors： Li LS,Morales JC,Veigl M,Sedwick D,Greer S,Meyers M,Wagner M,Fishel R,Boothman DA

更新日期：2009-10-01 00:00:00

abstract：:The uncoupling activity of oxyclozanide in warm blooded animals has been studied in whole animals, isolated tissue in vitro and on mitochondrial preparations. The onset of post mortem rigidity in mice and rats is accelerated and a contracture of striated muscle is produced. Oxyclozanide (1 muM) stimulated rat liver mi...

journal_title：British journal of pharmacology

authors： Veenendaal GH,de Waal MJ

更新日期：1974-03-01 00:00:00

abstract：:Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1...

journal_title：British journal of pharmacology

authors： Nickenig G,Strehlow K,Bäumer AT,Baudler S,Wassmann S,Sauer H,Böhm M

更新日期：2000-10-01 00:00:00

abstract：:The novel urotensin-II (U-II) receptor (UT) ligand, [Pen(5),DTrp(7),Dab(8)]U-II(4-11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to...

journal_title：British journal of pharmacology

authors： Camarda V,Spagnol M,Song W,Vergura R,Roth AL,Thompson JP,Rowbotham DJ,Guerrini R,Marzola E,Salvadori S,Cavanni P,Regoli D,Douglas SA,Lambert DG,Calò G

更新日期：2006-01-01 00:00:00

abstract：:The effect of adenosine on transepithelial ion transport was investigated in isolated preparations of murine trachea mounted in Ussing chambers. The possible regulation of adenosine receptors in an established model of allergic airway inflammation was also investigated. Mucosally applied adenosine caused increases in ...

journal_title：British journal of pharmacology

authors： Kornerup KN,Page CP,Moffatt JD

更新日期：2005-04-01 00:00:00

abstract：:1. To investigate the underlying mechanism for the angiotensin II-induced desensitization of the contractile response during the prolonged stimulation of the vascular smooth muscle, we determined the effects of angiotensin-II on (1) cytosolic Ca2+ concentration ([Ca2+]i) and tension using fura-2-loaded medial strips o...

journal_title：British journal of pharmacology

authors： Ushio-Fukai M,Yamamoto H,Toyofuku K,Nishimura J,Hirano K,Kanaide H

更新日期：2000-02-01 00:00:00

abstract：BACKGROUND AND PURPOSE:Although picrotoxin is a well-established antagonist of GABA(A) receptors, detailed studies of its action on inhibitory synaptic transmission have not previously been made. EXPERIMENTAL APPROACH:Electrophysiological techniques were used to study the action of picrotoxin on inhibitory postsynapti...

journal_title：British journal of pharmacology

authors： Korshoej AR,Holm MM,Jensen K,Lambert JD

更新日期：2010-02-01 00:00:00

abstract：:The protease inhibitor ritonavir is an integral part of current antiretroviral therapy targeting human immunodeficiency virus. Recent studies demonstrate that ritonavir induces apoptotic cell death with high efficiency in lymphoblastoid cell lines. Moreover, ritonavir can suppress activation of the transcription facto...

journal_title：British journal of pharmacology

authors： Mühl H,Paulukat J,Höfler S,Hellmuth M,Franzen R,Pfeilschifter J

更新日期：2004-12-01 00:00:00

abstract：BACKGROUND AND PURPOSE:Tumour cell migration and adhesion constitute essential features of metastasis. G-protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cance...

journal_title：British journal of pharmacology

authors： Kargl J,Andersen L,Hasenöhrl C,Feuersinger D,Stančić A,Fauland A,Magnes C,El-Heliebi A,Lax S,Uranitsch S,Haybaeck J,Heinemann A,Schicho R

更新日期：2016-01-01 00:00:00

abstract：:Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginin...

journal_title：British journal of pharmacology

authors： Ziessen T,Moncada S,Cellek S

更新日期：2002-01-01 00:00:00

abstract：:1. The vasodilator effects of arginine, nitric oxide (NO), acetylcholine (ACh) and sodium nitroprusside (NP) in the noradrenaline-preconstricted ('high tone') perfused rat kidney have been examined. 2. L-Arginine (0.6-23 mumol) caused a biphasic change in renal perfusion pressure. D-Arginine (0.6-23 mumol) was without...

journal_title：British journal of pharmacology

authors： Bhardwaj R,Moore PK

更新日期：1989-07-01 00:00:00

abstract：:To characterize the volume-sensitive, osmolyte permeable anion channels responsible for the osmodependent release of taurine from supraoptic nucleus (SON) astrocytes, we investigated the pharmacological properties of the [(3)H]-taurine efflux from acutely isolated SON. Taurine release induced by hypotonic stimulus (25...

journal_title：British journal of pharmacology

authors： Brès V,Hurbin A,Duvoid A,Orcel H,Moos FC,Rabié A,Hussy N

更新日期：2000-08-01 00:00:00

abstract：:1. The effects of cromakalim (BRL 34915) on the smooth muscle cells of guinea-pig mesenteric artery and vein were investigated with microelectrode and tension recording methods. 2. Cromakalim (greater than 10 microM) produced membrane hyperpolarization with an increase in ionic conductance. The hyperpolarization occur...

journal_title：British journal of pharmacology

authors： Nakao K,Okabe K,Kitamura K,Kuriyama H,Weston AH

更新日期：1988-11-01 00:00:00

abstract：:It was confirmed that morphine administration in vivo produced a selective decrease in the calcium content of synaptosomal fractions prepared from rat cerebral cortices. This effect was prevented by naloxone. 2 After morphine or naloxone, there were no changes in the sodium, potassium and magnesium contents of any of ...

journal_title：British journal of pharmacology

authors： Cardenas HL,Ross DH

更新日期：1976-08-01 00:00:00

abstract：:1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a...

journal_title：British journal of pharmacology

authors： Ishida H,Fujii E,Irie K,Yoshioka T,Muraki T,Ogawa R

更新日期：2000-07-01 00:00:00

abstract：:1. Single smooth muscle cells were isolated from bovine trachealis by enzymic digestion. The properties of large conductance plasmalemmal K(+)-channels in these cells were studied by the patch-clamp recording technique. 2. Recordings were made from inside-out plasmalemmal patches when [K+] was symmetrically high (140 ...

journal_title：British journal of pharmacology

authors： Green KA,Foster RW,Small RC

更新日期：1991-04-01 00:00:00

abstract：:The aim of the present study was to determine whether inhibition of cyclic nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was addressed by evaluating the effects of both nonselective and selective inhibitors of PDEs on...

journal_title：British journal of pharmacology

authors： Eskandari N,Wickramasinghe T,Peachell PT

更新日期：2004-08-01 00:00:00

abstract：:Bradykinin, angiotensin II, arginine vasopressin (AVP) or des-amino-D-arginine vasopressin (DDAVP) were administered by intravenous infusion to 10 healthy men. The concentration of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), the stable hydrolysis product of prostacyclin (PGI2), was measured in plasma using gas ch...

journal_title：British journal of pharmacology

authors： Barrow SE,Dollery CT,Heavey DJ,Hickling NE,Ritter JM,Vial J

更新日期：1986-01-01 00:00:00

abstract：:The past two decades have seen an immense increase in our appreciation of the vast range of signalling processes and supporting machinery that occur in cells. Pivotal to this is the notion of signal compartmentalization (compartmentation). Targeting by protein domains is critical in allowing signalling complexes to be...

journal_title：British journal of pharmacology

authors： Houslay MD

更新日期：2009-09-01 00:00:00

abstract：BACKGROUND AND PURPOSE:Palmitoylethanolamide (PEA) is an endogenous congener of anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and at transient receptor potential vanilloid type-1 (TRPV1) channels. The other endocannabinoid, 2-arachidonoylglycerol (2-AG), was recently suggested to act as a...

journal_title：British journal of pharmacology

authors： Petrosino S,Schiano Moriello A,Cerrato S,Fusco M,Puigdemont A,De Petrocellis L,Di Marzo V

更新日期：2016-04-01 00:00:00

abstract：:1. The effect of several metabotropic ligands and di- or tripeptides were tested on the binding of [3H]-L(+)-2-amino-4-phosphonobutyric acid ([3H]-L-AP4) on rat mGlu4 receptor. For selected compounds, the functional activity was determined on this receptor using the guanosine-5'[gamma-35S]-thiotriphosphate [gamma-35S]...

journal_title：British journal of pharmacology

authors： Monastyrskaia K,Lundstrom K,Plahl D,Acuna G,Schweitzer C,Malherbe P,Mutel V

更新日期：1999-11-01 00:00:00

abstract：:The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate in vitro was used for comparing atropine-like effects. Trazodone was found to have essentially no activity at the ...

journal_title：British journal of pharmacology

authors： Hyslop DK,Taylor DP

更新日期：1980-01-01 00:00:00

abstract：:1 Core and tail skin temperature was measured in rats which had guide cannulae implanted into their brains to allow drug injections directly into the preoptic anterior hypothalamus. 2 Apomorphine and dopamine (10 microgram in 1 microliter) injected into the area of the preoptic anterior hypothalamus caused a fall in c...

journal_title：British journal of pharmacology

authors： Cox B,Lee TF

更新日期：1977-09-01 00:00:00