Abstract：
BACKGROUND AND PURPOSE:We have previously shown that lipid mediators, produced by phospholipase D and C, are generated in OX(1) orexin receptor signalling with high potency, and presumably mediate some of the physiological responses to orexin. In this study, we investigated whether the ubiquitous phospholipase A(2) (PLA(2)) signalling system is also involved in orexin receptor signalling. EXPERIMENTAL APPROACH:Recombinant Chinese hamster ovary-K1 cells, expressing human OX(1) receptors, were used as a model system. Arachidonic acid (AA) release was measured from (3)H-AA-labelled cells. Ca(2+) signalling was assessed using single-cell imaging. KEY RESULTS:Orexins strongly stimulated [(3)H]-AA release (maximally 4.4-fold). Orexin-A was somewhat more potent than orexin-B (pEC(50) = 8.90 and 8.38 respectively). The concentration-response curves appeared biphasic. The release was fully inhibited by the potent cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate, whereas the iPLA(2) inhibitors, R- and S-bromoenol lactone, caused only a partial inhibition. The response was also fully dependent on Ca(2+) influx, and the inhibitor studies suggested involvement of the receptor-operated influx pathway. The receptor-operated pathway, on the other hand, was partially dependent on PLA(2) activity. The extracellular signal-regulated kinase, but not protein kinase C, were involved in the PLA(2) activation at low orexin concentrations. CONCLUSIONS AND IMPLICATIONS:Activation of OX(1) orexin receptors induced a strong, high-potency AA release, possibly via multiple PLA(2) species, and this response may be important for the receptor-operated Ca(2+) influx. The response coincided with other high-potency lipid messenger responses, and may interact with these signals.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Turunen PM,Ekholm ME,Somerharju P,Kukkonen JPdoi
10.1111/j.1476-5381.2009.00535.xsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
212-21issue
1eissn
0007-1188issn
1476-5381pii
BPH535journal_volume
159pub_type
杂志文章abstract：:The basis of the maternal to foetal serum concentration gradient of dexamethasone was investigated in the rat on day 20 of gestation. The pregnant rat was assumed to behave as a two-compartment open model with one maternal and one foetal pool exchanging with each other and each to outside. Bolus injections of unlabell...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb16254.x
更新日期：1986-08-01 00:00:00
abstract：:1 Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15-20 mg/kg) and atropine. The H2-receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra-arterially did not depress si...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07329.x
更新日期：1975-01-01 00:00:00
abstract：:1. Calcium entry via neuronal calcium channels is essential for the process of neurotransmission. We investigated the calcium channel subtypes involved in the operation of cardiac autonomic neurotransmission by examining the effects of selective calcium channel blockers on the inotropic responses to electrical field s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702629
更新日期：1999-06-01 00:00:00
abstract：:1. The sulphonylureas, tolbutamide (0.1-10 mM) and glibenclamide (0.1-100 microM) shown not to inhibit ATP-K+ channel currents when applied to inside-out membrane patches excised from rat cultured cerebral cortex or freshly-dispersed ventromedial hypothalamic nucleus (VMHN) neurones. 2. Saturable binding sites for [3H...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14116.x
更新日期：1990-11-01 00:00:00
abstract：:1. The effects of intradermally injected prostaglandins (PGs) E(1), E(2), F(1alpha) and F(2alpha) have been examined in the rat and in man.2. PGE(1) and PGE(2) caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb09934.x
更新日期：1971-01-01 00:00:00
abstract：:1. Depolarization of rat cerebral cortical slices, prelabelled with [3H]-histidine, in high potassium (40 mM KCl) medium stimulated the release of [3H]-histamine. The K+-evoked release of [3H]-histamine was attenuated by incubation in calcium-free medium and prevented by prior incubation of brain slices with the selec...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11758.x
更新日期：1988-12-01 00:00:00
abstract：:1. The present study was undertaken to investigate the effect of Delta9-tetrahydrocannabinol (Delta9-THC) and possible serotoninergic involvement on the extracellular level of dopamine (DA) in the striatum using microdialysis in conscious, freely-moving rats. 2. A dose-dependent increase in striatal DA release occurre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702753
更新日期：1999-09-01 00:00:00
abstract：:Expression of two isoforms of Rho-kinase (ROCK) and its functional role in the physiological control of smooth muscle contraction in the sheep ureter were investigated. Helical strips of the ureteric smooth muscle were stimulated by electrical field stimulation (EFS, 60 V, 1 mS, 2, 4, 8, 16 and 32 Hz, for 20 S), KCl (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705961
更新日期：2004-10-01 00:00:00
abstract：:Rats were placed on either a low sodium intake (low sodium diet 0.025% dry weight, tap water for drinking) or a high sodium intake (normal sodium diet 0.45% dry weight, 0.9% saline for drinking) for 10 days. The pressor-response curve to angiotensin II in rats previously on a high sodium intake was shifted to the left...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb11111.x
更新日期：1985-12-01 00:00:00
abstract：:The human distal gut is home to a rich and dense microbial community with representatives of all three domains of life which are intricately connected with our physiology and health. The combined genomes of these microbes, collectively called the human microbiome, vastly expand the metabolic capacities of our own geno...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14085
更新日期：2018-12-01 00:00:00
abstract：:1. In cultured endothelial cells of the pig the endothelium-derived relaxing factor (EDRF) releasing agent thrombin (2 u ml-1) caused a significant increase in basal levels of both guanosine 3':5'-cyclic monophosphate (cyclic GMP) and inositol 1,4,5-trisphosphate (IP3). This increase was time dependent, with peak leve...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12166.x
更新日期：1991-01-01 00:00:00
abstract：:1. Inhalational anaesthetics modulate ligand-gated ion channels at clinical concentrations. In this paper we address submolecular mechanisms for gamma-aminobutyric acid (GABA) receptor modulation by isoflurane. 2. Wild-type Drosophila melanogaster homo-oligomeric GABA receptors were characterized and compared with an ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701417
更新日期：1997-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 cri...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707116
更新日期：2007-02-01 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
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706438
更新日期：2006-01-01 00:00:00
abstract：:1. The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A1 adenosine receptor (A1 receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702287
更新日期：1999-01-01 00:00:00
abstract：:1. The NK1 tachykinin receptor agonists, septide, [Sar9,Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10-20 min) when injected intracerebroventricularly (i.c.v.) in the guinea-pig. The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 micrograms), compared to [Sar9,Met(O2)11]SP, whi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15101.x
更新日期：1995-11-01 00:00:00
abstract：:1. RS-15385-197 ((8aR, 12aS, 13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro- 3-methoxy-12-(methylsulphonyl)-6H-isoquino [2,1-g][1,6]-naphthyridine) was evaluated in a series of in vitro and in vivo tests as an antagonist at alpha 2-adrenoceptors. 2. RS-15385-197 had a pKi of 9.45 for alpha 2-adrenoceptors in the rat cor...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12834.x
更新日期：1993-02-01 00:00:00
abstract：:1. Inhibition of human polymorphonuclear leucocyte (PMN) function by adenosine was studied with respect to effects of adenosine on intracellular cyclic AMP and calcium during the PMN respiratory burst. 2. The adenosine analogue 5'-N-ethylcarboxamide-adenosine (NECA) and L-N6-phenyl-isopropyl-adenosine (L-PIA) inhibite...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12028.x
更新日期：1989-07-01 00:00:00
abstract：:1. The affinities of a number of alpha 1-adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha 1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affini...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15907.x
更新日期：1995-07-01 00:00:00
abstract：:1. A study was made to exclude the notion that adenosine receptor agonists exert a direct physical blockade of the depolarization-secretion process. Reduced temperature was employed as a tool for distinguishing between physico-chemical processes (such as those which mediate evoked transmitter release) and biochemical ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11470.x
更新日期：1988-04-01 00:00:00
abstract：:1. Block by philanthotoxin-343 (PhTX-343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage-clamp techniques. 2. In the cells held at -60 mV, PhTX-343 at 0.1 and 1 mic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701373
更新日期：1997-09-01 00:00:00
abstract：:1. Protein phosphorylation is involved in the induction of nitric oxide synthase II (NOS II, iNOS) in several types of animal cells. Here we have investigated the possible involvement of major protein kinases in the induction of NOS II expression in human DLD-1 cells. 2. In DLD-1 cells, interferon--gamma alone induced...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701782
更新日期：1998-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Recent studies suggest that the effects of cyclooxygenase-2 (COX-2) inhibition are mediated by cannabinoid receptor activation. However, some non-steroidal anti-inflammatory drugs inhibit the enzyme fatty acid amide hydrolase, which regulates levels of some endocannabinoids. Whether COX-2 directl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00703.x
更新日期：2010-06-01 00:00:00
abstract：:1. Prostaglandin E2 (PGE2) relaxes circular smooth muscle of the rabbit isolated jugular vein at very low concentrations (mean pIC50 against histamine-induced contraction = 9.34). This effect is not blocked by the EP1-receptor antagonist, AH 6809 (2 microM). 2. From a group of prostaglandin E analogues examined, 16,16...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09063.x
更新日期：1992-04-01 00:00:00
abstract：:1. The mechanisms by which nicorandil causes relaxation of rat isolated small mesenteric arteries mounted on a Mulvany myograph was investigated by use of a combination of putatively mechanism-specific antagonists. 2. In arteries precontracted by the thromboxane-mimetic, U46619, the EC50 for cromakalim and levcromakal...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb16071.x
更新日期：1996-12-01 00:00:00
abstract：:(1) 5-HT moduline (5-HTm) is tetrapeptide (Leu-Ser-Ala-Leu) previously shown to act as a specific endogenous antagonist to central 5-HT(1B/1D) receptors. Its effects were investigated in rat and rabbit pulmonary arteries (PAs). (2) In rabbit PAs, contractile responses to the 5-HT(1B/1D) receptor agonist 5-carboxamidot...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0705123
更新日期：2003-03-01 00:00:00
abstract：:1 The present study comprised treatment of healthy male rats with Delta(9)-tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days. 2 Upon 30-days chronic administrations, the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705015
更新日期：2003-01-01 00:00:00
abstract：:We investigated whether 10 days' in vivo treatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteries ex vivo and, if so, what the underlying mechanism might be. ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric ox...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706365
更新日期：2005-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhalation of the superantigen,staphylococcal enterotoxin B (SEB), leads to the activation of the host T and invariant natural killer (iNK) T cells, thereby resulting in acute lung inflammation and respiratory failure but the underlying mechanism(s) of disease remain elusive, with limited treatme...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02063.x
更新日期：2012-11-01 00:00:00
abstract：:1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an aff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07372.x
更新日期：1975-03-01 00:00:00
