Abstract:
:1. We have studied whether a nucleotide receptor mediates the effects of extracellular ATP and UTP on phosphatidylcholine metabolism in rat cultured glomerular mesangial cells. 2. ATP and UTP stimulated a biphasic 1,2-diacylglycerol (DAG) formation in [3H]-arachidonic acid-labelled mesangial cells. In contrast, in cells labelled with [3H]-myristic acid, a tracer that preferentially marks phosphatidylcholine, both nucleotides induced a delayed monophasic production of DAG with a concomitant increase in phosphatidic acid and choline formation. 3. A phospholipase D-mediated phosphatidylcholine hydrolysis was further suggested by the observation that ATP and UTP stimulate the accumulation of phosphatidylethanol, when ethanol was added to mesangial cells. 4. The rank order of potency of a series of nucleotide analogues for stimulation of phosphatidylethanol formation was UTP = ATP > ITP > ATP gamma S > beta gamma-imido-ATP = ADP > 2-methylthio-ATP = beta gamma-methylene-ATP = ADP beta S, while AMP, adenosine, CTP and GTP were inactive, indicating the presence of a nucleotide receptor. 5. Elevation of cytosolic free Ca2+ by the calcium ionophore A23187 (1 microM) or the Ca(2+)-ATPase inhibitor, thapsigargin (200 nM) slightly increased phosphatidylethanol formation. However, chelation of cytosolic Ca2+ with high concentrations of Quin 2 did not attenuate ATP- and UTP-induced phosphatidylethanol production, thus suggesting that Ca2+ is not crucially involved in agonist-stimulated phospholipase D activation. 6. The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), but not the biologically inactive 4 alpha-phorbol 12,13-didecanoate, increased phospholipase D activity in mesangial cells, suggesting that PKC may mediate nucleotide-induced phosphatidylcholine hydrolysis. 7. Down-regulation of PKC-alpha and -delta isoenzymes by 8 h PMA treatment still resulted in full phospholipase D activation. In contrast, a 24 h treatment of mesangial cells with PMA, a regimen that also causes depletion of PKC-epsilon, markedly attenuated nucleotide-evoked phosphatidylethanol formation. In addition, the selective PKC inhibitor, calphostin C attenuated ATP- and UTP-induced phosphatidylethanol production.8. In summary, these data suggest that extracellular ATP and UTP use a common nucleotide receptor to activate phospholipase D-mediated phosphatidylcholine hydrolysis. Stimulation of phospholipase D appears to involve the PKC-epsilon isoenzyme, activated by DAG derived from phosphoinositide hydrolysis by phospholipase C.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Pfeilschifter J,Merriweather Cdoi
10.1111/j.1476-5381.1993.tb13890.xsubject
Has Abstractpub_date
1993-10-01 00:00:00pages
847-53issue
2eissn
0007-1188issn
1476-5381journal_volume
110pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Venoms are a rich source of ligands for ion channels, but very little is known about their capacity to modulate G-protein coupled receptor (GPCR) activity. We developed a strategy to identify novel toxins targeting GPCRs. EXPERIMENTAL APPROACH:We studied the interactions of mamba venom fractions...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00532.x
更新日期:2010-01-01 00:00:00
abstract::The effects of high (20 mM) concentrations of caffeine were studied on the transmembrane voltage and currents in rat single ventricular myocytes by the whole cell configuration of the patch clamp technique. Rapid application of caffeine released Ca2+ from the sarcoplasmic reticulum and induced a Ni(2+)-sensitive trans...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13702.x
更新日期:1993-08-01 00:00:00
abstract::Endothelin-1 (ET-1) is a peptide hormone produced within the myocardium which may modulate myocardial contractility in a paracrine-autocrine fashion. In the majority of species, ET-1 has a direct positive inotropic effect on the myocardium that involves both increased myofilament Ca(2+) sensitivity and increased Ca(2+...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1038/sj.bjp.0707438
更新日期:2007-10-01 00:00:00
abstract::1 Physiologically, perisinusoidal hepatic stellate cells (HSC) are quiescent and store retinoids. During liver injury and in cell culture, HSC transform into proliferating myofibroblast-like cells that express alpha-smooth muscle actin (alpha-sma) and produce excessive amounts of extracellular matrix. During transform...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705303
更新日期:2003-06-01 00:00:00
abstract::G protein-coupled receptors are one of the most actively studied families of proteins. However, despite the ubiquity of protein dimerization and oligomerization as a structural and functional motif in biology, until the last decade they were generally considered as monomeric, non-interacting polypeptides. For the meta...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707490
更新日期:2008-03-01 00:00:00
abstract::1. The present study was designed to evaluate the nature of intervening agents in L-DOPA- and dopamine-induced neurotoxicity in Neuro-2A cells. 2. In the absence of cells and in conditions of light protection, at 37 degrees C, L-DOPA or dopamine (1 mM) in culture medium degraded spontaneously in a time-dependent manne...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704982
更新日期:2002-12-01 00:00:00
abstract::A dispersed rat anterior pituitary cell system has been used to investigate the effects of cyproheptadine and metergoline on prolactin secretion. Both drugs were potent inhibitors of prolactin secretion. However, the inhibition was not antagonized by either 5-hydroxytryptamine or a variety of dopamine antagonists. We ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10896.x
更新日期:1980-09-01 00:00:00
abstract::1. Endothelin-1 (ET-1) binding site densities and constrictor activities were compared in airway smooth muscle preparations of human, guinea-pig, rat and mouse. 2. The mean contractile response to 0.3 microM ET-1 (measured as the % maximum response to 10 microM carbachol, % Cmax +/- s.e.mean) and the mean concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14093.x
更新日期:1990-08-01 00:00:00
abstract::1. The single-channel current recording technique has been used to investigate the effects of cromakalim, diazoxide and ATP, separately and combined, on the opening of ATP-sensitive potassium channels in the insulin-secreting cell-line RINm5F. The actions of these drugs have been studied using the permeabilized open-c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14672.x
更新日期:1990-01-01 00:00:00
abstract::1. Besides its antimuscarinic effects, propiverine may possess an additional mode of action. We compared the effects of propiverine, three of its metabolites (M-5, M-6, M-14) and atropine in human, pig and mouse urinary bladder preparations in order to elucidate the nature of a possible additional mode of action. 2. L...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706244
更新日期:2005-07-01 00:00:00
abstract::1. The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were investigated by use of whole-cell and outside-out patch clamp techniques. 2. NDGA (5-50 microM) produced a concentration-dependent inhibition of whole-cell K+ currents at all activa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701452
更新日期:1997-11-01 00:00:00
abstract::1. Anaesthetized, open-chest dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 90 min of reperfusion. Endothelium-dependent and -independent relaxant responses of the isolated coronary arterial rings were then investigated. 2. The endothelium-dependent, acetylcholine-induced relaxa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09018.x
更新日期:1992-03-01 00:00:00
abstract::1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706789
更新日期:2006-07-01 00:00:00
abstract::1. We have taken advantage of our recent development of highly potent and specific phosphinic inhibitors of endopeptidase 3.4.24.15 to examine the putative contribution of the enzyme in the secretion of A beta by HK293 transfected cells overexpressing the wild type and the Swedish (Sw) double mutated form of beta APP7...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701151
更新日期:1997-06-01 00:00:00
abstract::1. Inositol phospholipid hydrolysis was examined in human cerebral cortex slices by a [3H]-inositol prelabelling assay. 2. Enhancement of [3H]-inositol phosphates accumulation was observed in the presence of carbachol, noradrenaline, histamine, 5-hydroxytryptamine (5-HT) and depolarizing concentrations of KCl. 3. Desp...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12048.x
更新日期:1990-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The histamine H4 receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00236.x
更新日期:2009-05-01 00:00:00
abstract::1. Antidepressant drugs are known to inhibit some changes evoked by glucocorticoids, as well as a hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, often observed in depression. 2. The aim of present study was to investigate effects of various antidepressant drugs on the glucocorticoid-mediated gene transcri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703445
更新日期:2000-07-01 00:00:00
abstract::1. An investigation has been made in rats into the neurotoxic effect of the relatively selective 5-hydroxytryptamine (5-HT) neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') using chlormethiazole and dizocilpine, both known neuroprotective compounds and also gamma-butyrolactone, ondansetron and pentoba...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14034.x
更新日期:1994-01-01 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
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11707.x
更新日期:1988-11-01 00:00:00
abstract::The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk be...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702219
更新日期:1998-12-01 00:00:00
abstract::1. The purpose of this study was to determine if corpus cavernosum smooth muscle expresses functional postsynaptic alpha2-adrenoceptors (AR). 2. The alpha2-adrenoceptor agonist UK 14,304 elicited concentration-dependent contractions in rabbit corpus cavernosum smooth muscle (CCSM). The half-maximal response occurred a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701739
更新日期:1998-03-01 00:00:00
abstract::There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705480
更新日期:2003-10-01 00:00:00
abstract::1. The effects of some chloride channel antagonists were studied on the calcium-activated chloride current (ICl(Ca)) in smooth muscle cells from the rabbit portal vein with the perforated patch technique. 2. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and 4,4'-diisothiocyanato-stilbene-2,2'-disu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14891.x
更新日期:1994-04-01 00:00:00
abstract::Irritable bowel syndrome is characterized by visceral hyperalgesia commonly associated with stress and inflammatory processes. We investigated the role of tachykinin NK2 receptors in the ability of trinitrobenzenesulphonic acid (TNBS) and stress to enhance the sensitivity of the rat rectum to distension using a select...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703040
更新日期:2000-01-01 00:00:00
abstract::1. Ethanol has been reported to inhibit the induction of long-term potentiation (LTP) in the hippocampus. However, the correlation between the effects of ethanol in vivo and in vitro remained unclear. In addition, previous works have little considered the possibility that the effect of ethanol is mediated by its metab...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702738
更新日期:1999-08-01 00:00:00
abstract::1. DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane hydrochloride (M & B 17803A) was given to four healthy volunteers in single oral doses of up to 300 mg. There were no subjective effects and no significant alterations in the heart rate, systolic and diastolic blood pressure in the seated posit...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1476-5381.1971.tb07193.x
更新日期:1971-11-01 00:00:00
abstract::1. The effect of the novel ET(A) receptor antagonist LBL 031 and other selective and mixed endothelin receptor antagonists on endothelin-1 (ET-1)-induced and lipopolysaccharide (LPS)-induced microvascular leakage was assessed in rat airways. 2. Intravenously administered ET-1 (1 nmole kg(-1)) or LPS (30 mg kg(-1)) cau...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703691
更新日期:2000-11-01 00:00:00
abstract::An investigation of the effects of gamma-aminobutyric acid (GABA) and the selective GABAB receptor agonist, baclofen, on basal and stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in slices of rat cerebral cortex has been carried out. Neither GABA nor baclofen produced any significant change in basa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::1. The effects of some drugs known to inhibit transmission in the superior cervical ganglion and at the neuromuscular junction were investigated on the cholinergic nerve-smooth muscle junction, using the rat isolated innervated urinary bladder preparation.2. HC-3 and Win 4981 inhibited the indirectly evoked contractio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09900.x
更新日期:1970-08-01 00:00:00
abstract::1. The modulation of the gamma-aminobutyric acidA (GABAA) receptor by reduced metabolites of progesterone and deoxycorticosterone has been compared with that produced by depressant barbiturates in: (a) voltage-clamp recordings from bovine enzymatically isolated chromaffin cells in cell culture, and (b) an assay of the...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11646.x
更新日期:1988-08-01 00:00:00