Abstract:
:1. mu-Opioid receptor agonists mediate their central analgesic effects by actions on neurons within brain regions such as the mid-brain periaqueductal grey (PAG). Within the PAG, mu-opioid receptor-mediated analgesia results from inhibition of GABAergic influences on output projection neurons. We have established that mu-opioid receptor activation in the PAG causes a presynaptic inhibition of GABA release that is mediated by activation of a voltage-dependent K+ channel via 12-lipoxygenase (LOX) metabolites of arachidonic acid. 2. At a cellular level, mu-opioid agonists have also been shown to open inwardly rectifying K+ channels, close voltage-gated Ca2+ channels and presynaptically inhibit glutamatergic synaptic transmission in the PAG. 3. The mu-opioid receptor-mediated presynaptic inhibition of GABAergic transmission was abolished by phospholipase A2 inhibitors and non-specific LOX and specific 12-LOX inhibitors. Cyclo-oxygenase (COX) and specific 5-LOX inhibitors did not reduce the inhibitory effects of mu-opioid agonists. 4. The opioid actions on GABAergic transmission were mimicked by arachidonic acid and 12-LOX metabolites, but not 5-LOX metabolites. The efficacy of mu-opioids was enhanced synergistically by treatment of PAG neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism, COX and 5-LOX. 5. These results explain a previously described analgesic action of COX inhibitors in the central nervous system that was both independent of prostanoid release and inhibited by opioid receptor antagonists and they also explain the synergistic interaction of opioids with COX inhibitors. These findings also suggest new avenues for the development of centrally active analgesic agents involving combinations of lowered doses of opioids and specific 5-LOX inhibitors.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Christie MJ,Connor M,Vaughan CW,Ingram SL,Bagley EEdoi
10.1046/j.1440-1681.2000.03291.xkeywords:
subject
Has Abstractpub_date
2000-07-01 00:00:00pages
520-3issue
7eissn
0305-1870issn
1440-1681journal_volume
27pub_type
杂志文章,评审abstract::We evaluated the role of deferasirox therapeutic drug monitoring in order to avoid toxicity or treatment failure. Plasma concentrations, measured between two consecutive liver iron determinations, were determined at the end of dosing interval. Fifty-four β-thalassemic adult patients were enrolled: 50% were males; medi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12879
更新日期:2018-02-01 00:00:00
abstract::1. Infusion of salbutamol (3.0 microgram/min after a bolus injection of 100 microgram) produced hypokalaemia in conscious dogs. 2. Measurement of arterial and coronary sinus potassium differences revealed no significant potassium loss from the heart with established hypokalaemia. 3. Shortly after the initial salbutamo...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1978.tb00717.x
更新日期:1978-11-01 00:00:00
abstract::Based on 28 reported patients, constant features of the syndrome of hypertension and hyperkalaemia are hyperkalaemia, hyperchloraemia, normal renal glomerular function and, in all adult patients, hypertension. Inconstant features include short stature, intellectual impairment and muscle weakness. Levels of renin and a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00358.x
更新日期:1986-04-01 00:00:00
abstract::1. Clinical pharmacology requires numerous skills and most activities involve interactions with other specialities, both clinical and experimental. 2. A range of experts has had a major influence on the nature and design of my research, which is illustrated by the evolution of my knowledge of adverse drug reactions an...
journal_title:Clinical and experimental pharmacology & physiology
pub_type:
doi:10.1046/j.1440-1681.2001.03542.x
更新日期:2001-11-01 00:00:00
abstract::1. In rats, inhibition of type IV phosphodiesterase (PDE4) attenuates acute renal failure and early (hours) mortality induced by high-dose endotoxin. Because it is unlikely that protection of renal function accounts for improved early survivability, most likely PDE4 inhibition exerts multiple beneficial effects in end...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03332.x
更新日期:2000-10-01 00:00:00
abstract::1. The concentrations of gamma-amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days. 2. At the end of the treatment, birds on the small dose of FZ or NF lost about 9% of their bod...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01042.x
更新日期:1988-12-01 00:00:00
abstract::1. Prenatal dexamethasone leads to low birth weight and compromises organogenesis, but its effects on nephrogenesis in male and female rats have not yet been investigated extensively. Reduced renal mass may be responsible for hypertension and renal haemodynamic and morphological adjustments to maintain the glomerular ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03787.x
更新日期:2003-01-01 00:00:00
abstract::1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05548.x
更新日期:2011-08-01 00:00:00
abstract::1. Glyceryl trinitrate (GTN) is frequently infused intravenously as a component of the management of acute coronary syndromes (ACS). Abrupt cessation of GTN infusion after periods of more than 24 h administration often induces rebound vasoconstriction reflecting 'pseudotolerance'; this is also the basis of the 'zero h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1440-1681.2005.04182.x
更新日期:2005-04-01 00:00:00
abstract::1. It has been demonstrated that blood pressure variability (BPV) is increased in hypertension and related to organ damage. It will be important to lower BPV in the treatment of hypertension. The present study was designed to investigate the effect of ketanserin, a 5-HT2A receptor antagonist with a weak alpha1-adrenoc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03809.x
更新日期:2003-03-01 00:00:00
abstract::1. The effect of endothelin-1 on the release of adrenal catecholamines was examined in anaesthetized dogs. 2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz was applied before and after the intravenous injection of endothelin-1. 3. Endothelin-1 (0.1 and 0.3 micrograms/kg) significantly enhanced the release of adrena...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00519.x
更新日期:1992-09-01 00:00:00
abstract::1. Physical movement is accompanied by coordinated changes in respiratory and cardiovascular activity proportional to the metabolic demands of the locomotor task. Cardiorespiratory changes include increases in ventilation, blood pressure and heart rate, as well as altered regional sympathetic nerve activity and blood ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2002.03610.x
更新日期:2002-01-01 00:00:00
abstract::Previous studies have shown that endothelin (ET)-1 stimulates thromboxane (Tx)A(2) production and so we hypothesized that inhibiting prostanoid TP receptors would prevent the pressor and intrarenal haemodynamic response to an acute infusion of ET-1. 2. Male Sprague-Dawley rats were anaesthetized with Inactin (Sigma Ch...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04354.x
更新日期:2006-03-01 00:00:00
abstract::1. Tissue plasminogen activator (tPA) has both fibrinolytic and anti-inflammatory activity. These properties may be useful in treating inflammatory lung diseases, such as acute respiratory distress syndrome (ARDS). 2. We have previously demonstrated the feasibility of targeted pulmonary delivery of tPA. As part of our...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05011.x
更新日期:2008-12-01 00:00:00
abstract::1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hy...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01030.x
更新日期:1988-11-01 00:00:00
abstract::1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevat...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02433.x
更新日期:1994-01-01 00:00:00
abstract::Short-term salt loading and salt restriction in a group of normal pregnant women produced no changes in lying, sitting or standing blood pressures or heart rates. Home blood pressures showed no trend to change over the periods of altered salt intake. Although plasma volume and plasma renin activity changed with altere...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1985.tb02654.x
更新日期:1985-05-01 00:00:00
abstract::1. Anoxic perfusion of the isolated rat heart releases noradrenaline in the absence of sympathetic nerve fibre stimulation. 2. Anoxic noradrenaline release is enhanced by reducing the extracellular Na+ concentration, consistent with the proposal that such release occurs by carrier-mediated efflux. 3. Release is also e...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01375.x
更新日期:1991-01-01 00:00:00
abstract::1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle. 2. Ethionine does not cause changes in the blood parameters, including total plasma iron-binding capacity and plasma iron clearance. Erythrocyte...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb01851.x
更新日期:1975-11-01 00:00:00
abstract::1. The spinal sympathetic outflow (C7-T2) of pithed male Wistar rats was electrically stimulated (30-50 V, 0.5 ms, 0.1-1.0 Hz) and heart rate and arterial blood pressure were recorded. D-Tubocurarine (1 mg/kg) and atropine (1 mg/kg) were administered intravenously (i.v.) to reduce voluntary and parasympathetic nerve a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01036.x
更新日期:1988-12-01 00:00:00
abstract::1. The therapeutic effect of green tea extract (GTE) on the aortic collagen content and its characteristics were investigated in streptozotocin diabetic rats. 2. Diabetes was induced in rats by a single intra peritoneal injection of streptozotocin (60 mg/kg bodyweight). Six weeks after diabetes induction, GTE was admi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04374.x
更新日期:2006-04-01 00:00:00
abstract::1. Electrolytic lesions were made in various brain regions of the rat, and the effects of these lesions on nociceptive threshold and the antinociceptive actions of morphine were tested using a shock titration technique. 2. Lesions in the medial thalamus, the periaqueductal grey area, or the caudate nucleus, had no eff...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb03031.x
更新日期:1975-05-01 00:00:00
abstract::1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. T...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb01194.x
更新日期:1997-05-01 00:00:00
abstract:: NADPH oxidases (Nox) are reactive oxygen species (ROS)-generating enzymes that play important physiological roles in host defence and redox signalling. However, Nox activity is upregulated in the vascular wall during atherosclerosis and contributes to plaque formation by promoting oxidative stress and inflammation. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05657.x
更新日期:2012-03-01 00:00:00
abstract::1. Positive inotropic effect of taurine and improvement of cardiac performance of failing heart are mediated through the modulation of Ca2+ movement through the sarcolemma. 2. Cardioprotection with glutamate and aspartate is related to enhanced anaerobic energy formation in mitochondria coupled with succinate formatio...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb01748.x
更新日期:1996-08-01 00:00:00
abstract::1. The alpha-adrenoceptor antagonist, phentolamine, was administered intravenously, to conscious or anaesthetized rats, before or after the beta-adrenoceptor antagonist, propanolol. 2. The bradycardia which followed the combined administration of propranolol and phentolamine exceeded that induced by propranolol alone,...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00067.x
更新日期:1980-03-01 00:00:00
abstract::Preterm birth (PTB) is the single largest cause of death in infants and young children. The rate of PTB is significantly higher in male infants, particularly those that are born very preterm. Here we present evidence to suggest that the decidual renin-angiotensin system may play a role in inhibiting inflammation and m...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12734
更新日期:2017-05-01 00:00:00
abstract::1. Landrace swine were identified as malignant hyperpyrexia susceptible (MHS) or control by the contracture responses of gracilis muscle fibre bundles to 3% halothane, 2 mmol/l caffeine and 80 mmol/l KCl. The effects of calmodulin-antagonist drugs on the contractile behaviour of control and MHS preparations were inves...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01103.x
更新日期:1988-06-01 00:00:00
abstract::In an attempt to study the effects of thyroid hormones, antithyroid drugs and iodide on the conversion of thyroxine (T4) to triiodothyronine (T3), the liver was obtained from normal, hypothyroid and hyperthyroid rats treated with T4 or T3 . T4 was incubated with liver homogenates and generated T3 was measured. 1. The ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1981.tb00154.x
更新日期:1981-05-01 00:00:00
abstract::1. The concentration of methylguanidine and guanidinosuccinic acid has been measured in normal human plasma and discrepancies between various published methods for measuring methylguanidine have been resolved. Previous methods have been modified to allow these guanidines, together with guanidinoacetic acid and creatin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1978.tb00654.x
更新日期:1978-01-01 00:00:00