Abstract:
:1. Nociceptin, the endogenous ORL(1) receptor agonist inhibited the motor response to electrical-field stimulation in the rat anococcygeus muscle. This effect was characterized using the peptide ligands acetyl-Arg-Tyr-Tyr-Arg-Trp-Lys-NH(2) (Ac-RYYRWK-NH(2)), acetyl-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)) and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) ([F/G]NC(1-13)NH(2)), and the non-selective opioid antagonist naloxone benzoylhydrazone (NalBzOH). 2. Nociceptin produced a concentration-dependent inhibition of the adrenergic motor response to electrical-field stimulation (EC(50) 19 nM, pEC(50) 7.7+/-0.1, n=8), but the response to exogenous noradrenaline (0.2 - 1 microM) was unaffected. The inhibitory nerve response was not affected by up to 1 microM nociceptin. 3. After inhibition of nitric oxide synthase (N(omega)-nitro-L-arginine 100 microM), and in the presence of peptidase inhibitors, nociceptin produced full inhibition of the pure adrenergic motor response (EC(50) 4 nM; pEC(50) 8.4+/-0.1, E(max) 98.3+/-1.2%, n=12). Ac-RYYRWK-NH(2) was a potent partial-agonist (pEC(50) 9.0+/-0.1, E(max) 66.4+/-5.2; n=11) but the efficacy of Ac-RYYRIK-NH(2) (pEC(50) 8.0+/-0.2, E(max) 36.7+/-3.5; n=12) was lower and the peptide could be tested as an antagonist (pA(2) 9.01). 4. [F/G]NC(1-13)NH(2) and NalBzOH had little or no efficacy and were competitive antagonists with pK(B) values of 7.4 (95% c.l. 7.1, 7.7) and 6.9 (95% c.l. 6.7, 7.1) respectively. Both increased the response to field stimulation at high concentrations, suggesting the release of an endogenous agonist for the ORL(1) receptor during stimulation. 5. Rat nocistatin did not affect the response to electrical-field stimulation, nor did it modify the inhibitory action of nociceptin. 6. Our findings suggest there is a significant endowment of ORL(1) receptors on sympathetic terminals of the rat anococcygeus, where nociceptin mediates a powerful inhibitory effect on adrenergic neuromuscular transmission.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ho M,Corbett AD,McKnight ATdoi
10.1038/sj.bjp.0703583subject
Has Abstractpub_date
2000-09-01 00:00:00pages
349-55issue
2eissn
0007-1188issn
1476-5381journal_volume
131pub_type
杂志文章abstract::1. Exposure of depilated skin of guinea-pig to ultraviolet (u.v.) light for 20 s produces a prolonged inflammatory response.2. The erythaema becomes evident within 15-30 min after the exposure and progressively increases in intensity reaching its maximum by 4-6 hours. The erythaema persists over 24 hours.3. Increase i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08321.x
更新日期:1973-02-01 00:00:00
abstract::An approximate eight fold desensitization of the circular coat of the distal rabbit colon to adenosine 5'-triphosphate (ATP) and adenosine could be achieved by repeatedly exposing the organ to relatively low concentrations (10-100 microM) of these compounds. The desensitization was specific and reversible after prolon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08788.x
更新日期:1982-02-01 00:00:00
abstract::1 Acetylcholine, substance P, prostaglandin E1 and the nitrovasodilator glyceryl trinitrate induced concentration-dependent relaxations of endothelium-intact strips of rabbit coeliac artery precontracted with noradrenaline. 2 Endothelium-denuded strip preparations contracted to acetylcholine and showed no response to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11317.x
更新日期:1987-09-01 00:00:00
abstract::A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fund...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14499
更新日期:2019-11-01 00:00:00
abstract::1 The effects of indomethacin and eicosa-5,8,11,14-tetraynoic acid (ETYA) on the contractile response of the transmurally stimulated rabbit portal vein were studied in vitro.2 When the veins were stimulated for 240 pulses at 1 and 2 Hz, the responses were potentiated by indomethacin and ETYA. However, responses to 4 a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09687.x
更新日期:1974-09-01 00:00:00
abstract::1. Systemic infusion of neuropeptide Y (NPY) reduces renal blood flow and can concomitantly increase diuresis, natriuresis and calciuresis in anaesthetized rats. The present study was designed to investigate whether the apparently contradictory NPY effects on renal blood flow and urine formation and composition are me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701028
更新日期:1997-04-01 00:00:00
abstract::1. Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture. 2. Melatonin (10(-15) to 10(-13) M) induced pigment granule condensation; it was 10,000 times more effective than any ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07554.x
更新日期:1977-12-01 00:00:00
abstract::1. Heat stress (HS) is known to protect against myocardial ischaemia-reperfusion injury by improving mechanical dysfunction and decreasing necrosis. However, the mechanisms responsible for this form of cardioprotection remain to be elucidated. ATP-sensitive potassium (K(ATP)) channels have been shown to be involved in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701710
更新日期:1998-03-01 00:00:00
abstract::In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new ...
journal_title:British journal of pharmacology
pub_type: 社论
doi:10.1111/j.1476-5381.2009.00366.x
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Proteinase activated receptor 2 (PAR2) is a GPCR associated with inflammation, metabolism and disease. Clues to understanding how to block PAR2 signalling associated with disease without inhibiting PAR2 activation in normal physiology could be provided by studies of biased signalling. EXPERIMENT...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12757
更新日期:2014-09-01 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. Changes induced in the electrocorticogram by the bilateral perfusion of (+)-amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations. 2. (+)-Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08424.x
更新日期:1977-11-01 00:00:00
abstract::1. The effects of several agonists of the metabotropic glutamate receptor (mGluR) were studied in adult rat striatal slices by measuring (i) KCl (30 mM)-induced output of previously taken up D-[3H]-aspartate (Asp), (ii) forskolin (30 microM)-induced adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation and (i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13977.x
更新日期:1993-12-01 00:00:00
abstract::1. In order to explore whether 5-HT4 receptor subtypes exist, we have characterized further the 5-HT4 receptor that mediates tachycardia in the piglet isolated right atrium. All experiments were carried out in the presence of propranolol (400 nM) and cocaine (6 microM). We used tryptamine derivatives, substituted benz...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13916.x
更新日期:1993-11-01 00:00:00
abstract::1. The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels. 2. Dose-mean arterial pressu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14290.x
更新日期:1992-05-01 00:00:00
abstract::1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15198.x
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:NO-mediated, endothelium-dependent relaxations of isolated arteries are blunted by ageing and high-fat diets, as well as by apolipoprotein E deletion. The present study was designed to test the hypothesis that apolipoprotein E deletion impairs endothelium-dependent responses to prostacyclin (IP) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14386
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASS...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12193
更新日期:2013-07-01 00:00:00
abstract::By implanting a Teflon chamber subcutaneously into a sheep a mild aseptic inflammatory lesion was produced from which wound fluid could be sampled daily. The prostaglandin content of this wound fluid was examined. Prostaglandin E2 activity was found in all samples, and a peak was apparent on the fourth or fifth day af...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07363.x
更新日期:1975-02-01 00:00:00
abstract::Injection of carrageenan 1% (50 microl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old, weighing 32-34 g, displayed a consistent response in both phases. In 8-week-old mice, myeloper...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705650
更新日期:2004-05-01 00:00:00
abstract::1. We investigated the effect of KB-R7943, a Na(+)/Ca(2+) exchange inhibitor, on the aggregation response induced by adrenaline and 5-hydroxytryptamine (5-HT), alone or in combination in human and rabbit platelets in the presence or absence of ouabain. 2. KB-R7943 inhibited aggregation induced by the combination of ad...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703928
更新日期:2001-04-01 00:00:00
abstract::1. We investigated the mechanism of action of two novel nonsulphonylurea ATP-sensitive potassium channel (K(ATP)) inhibitors, PNU-99963 and PNU-37883A, on four types of cloned K(ATP) channels. 2. Whole-cell currents were recorded in a symmetrical potassium (140 mM) gradient in HEK-293 cells stably expressing Kir6.2/SU...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705228
更新日期:2003-05-01 00:00:00
abstract::(1) Stimulation of the vanilloid receptor-1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. (2) Recently, iodo-resiniferatoxin (I-RTX) has been reported ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705110
更新日期:2003-03-01 00:00:00
abstract::RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xeno...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702488
更新日期:1999-05-01 00:00:00
abstract::1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2. In these smooth muscle cells, ACh (0.1 and 1 microM) depolarized the membrane in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16642.x
更新日期:1995-08-01 00:00:00
abstract::A method is described for the determination of halothane-induced sleeping time in the rat. 2 The sleeping time exhibited a diurnal variation which was due, at least in part, to a change in the sensitivity of the central nervous system (CNS) to the anaesthetic. 3 Tolerance to halothane did not develop in rats repeatedl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07689.x
更新日期:1976-09-01 00:00:00
abstract::ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14645.x
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We previously demonstrated that chronic hyperinsulinaemia induced by drinking high levels of fructose augments adrenergic nerve-mediated vasoconstriction and suppresses vasodilatation mediated by calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. In this study, the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.8
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inflammasomes are multimeric complexes that facilitate caspase-1-mediated processing of the pro-inflammatory cytokines IL-1β and IL-18. Clinical hypertension is associated with renal inflammation and elevated circulating levels of IL-1β and IL-18. Therefore, we investigated whether hypertension i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13230
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibitory junction potentials (IJP) are responsible for smooth muscle relaxation in the gastrointestinal tract. The aim of this study was to pharmacologically characterize the neurotransmitters [nitric oxide (NO) and adenosine triphosphate (ATP)] and receptors involved at the inhibitory neuromus...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00454.x
更新日期:2009-11-01 00:00:00