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::1. The aim of the present study was to examine the effect of bacterial lipopolysaccharide (LPS) on the disposition of an organic anion transporting polypeptide and P-glycoprotein substrate in the rat isolated perfused liver. 2. Male Sprague-Dawley rats were divided into four groups. Three of the groups received 1, 2.5...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04419.x
更新日期:2006-08-01 00:00:00
abstract::1. While it is believed that the mammalian distal nephron is not involved in uric acid transport, this has not been directly evaluated. Nevertheless, some studies are consistent with significant distal nephron transport. 2. As uric acid transport in man may be similar to the rat, undirectional uric acid permeability w...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb02123.x
更新日期:1997-09-01 00:00:00
abstract::Ulcerative colitis is a major form of inflammatory bowel disease and increases the risk of the development of colorectal carcinoma. The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) make them promising tools for treating immune-mediated and inflammatory diseases. However, the lack o...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12321
更新日期:2015-01-01 00:00:00
abstract::1. Indices quantifying blood pressure (BP) and heart rate (HR) variability have been recently developed and may be used to assess the contribution of the autonomic nervous system to cardiovascular fluctuations. 2. Cardiovascular variables were measured in eight conscious mice equipped with a BP telemetric device. Each...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04895.x
更新日期:2008-04-01 00:00:00
abstract::This study describes the pharmacodynamic interaction between propofol and remifentanil. Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/1440-1681.12677
更新日期:2017-01-01 00:00:00
abstract::The prostaglandin synthesis inhibitor diclofenac sodium has been compared with a placebo in the treatment of primary nocturnal enuresis in a double-blind crossover trial. Twenty patients were entered: 14 female, six male; age range 6-17 years. The results showed that diclofenac sodium was significantly more effective ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1440-1681.1986.tb00327.x
更新日期:1986-02-01 00:00:00
abstract::1. Arterial baroreflexes are suppressed in stressful conditions. Intense visual stimuli can cause a threatening sensation and produce defensive reactions. 2. The present study was designed to determine whether and how electrical stimulation of the optic tract (OT) affects arterial baroreflexes, especially the heart ra...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03509.x
更新日期:2001-09-01 00:00:00
abstract::1. An antisense oligonucleotide (ASO) is a short strand of deoxyribonucleotide analogue that hybridizes with the complementary mRNA in a sequence-specific manner via Watson-Crick base pairing. Formation of the ASO-mRNA heteroduplex either triggers RNase H activity, leading to mRNA degradation, induces translational ar...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2006.04403.x
更新日期:2006-05-01 00:00:00
abstract::1. Telomeres (ends of chromosomes) undergo constant remodelling during cell development, proliferation and differentiation, as well as in neoplastic cell immortalization and transformation. How the cellular microenvironment influences telomere remodelling (lengthening or shortening) remains largely unknown. 2. Recentl...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05251.x
更新日期:2010-01-01 00:00:00
abstract::1. Ambulatory monitoring provides a unique opportunity for studying the temporal relationships between lifestyle factors and blood pressure (BP). These include physical activity, mental activity, environmental stressors, substances ingested for pleasure such as smoking, alcohol and caffeine, and nutrition. 2. Changes ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb01986.x
更新日期:1995-03-01 00:00:00
abstract::The purpose of the present study was to identify the differential proteins that synchronously change in urine and glomeruli and could be used to monitor glomerular lesions of IgA nephropathy (IgAN). The proteomes of urine and glomeruli from four IgAN patients who were graded III/IV according to the grading system of L...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12733
更新日期:2017-05-01 00:00:00
abstract::1. The aim of the present study was to evaluate the usefulness and reliability of a portable indirect calorimeter (Metavine; Vine, Tokyo, Japan). 2. We measured energy expenditure (EE) of elderly people (n = 191) at nursing homes using both Metavine and an authorized indirect calorimeter (Deltatrac Metabolic Monitor; ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.29.s4.6.x
更新日期:2002-10-01 00:00:00
abstract::1. The distribution of binding sites for [125I]-labelled endothelin-1 ([125I]-ET-1) and [125I]-labelled sarafotoxin S6B ([125I]-SRT) was visualized in rat tissues using in vitro autoradiography. 2. A high density of endothelin-1 (ET-1) binding was found in the heart. In the kidney, ET-1 binding occurred in association...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01485.x
更新日期:1991-07-01 00:00:00
abstract::1. Although measuring the rate of firing of multi-unit muscle sympathetic nerve activity (MSNA) has provided important information in many aspects of cardiovascular medicine, measuring single-unit vasoconstrictor activity provides a better understanding of the possible mechanisms underlying disturbed sympathetic nervo...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2008.04905.x
更新日期:2008-04-01 00:00:00
abstract::1. The hypothesis that adrenocorticotrophin (ACTH)-induced hypertension is a consequence of steroid-induced hyperinsulinaemia was tested using the somatostatin analogue (sandostatin, octreotide) to inhibit insulin release in Sprague-Dawley (SD) rats (n = 41). 2. Octreotide (20 micrograms, twice daily) did not modify b...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01647.x
更新日期:1993-10-01 00:00:00
abstract::1. Poor perfusion of the kidneys and gut, and associated functional impairment, are major problems in the first days of life in very preterm infants. These complications can be associated with a substantial mortality and further problems such as reduced kidney growth and chronic renal problems in later childhood. 2. T...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2006.04364.x
更新日期:2006-04-01 00:00:00
abstract::1. Patients with chronic kidney disease (CKD) demonstrate a high burden of vascular disease. This vascular disease is unusual by way of a preponderance of medial calcification. Further, traditional cardiovascular risk factors fail to fully explain the high cardiovascular event rate in this population. 2. The present r...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2007.04660.x
更新日期:2007-07-01 00:00:00
abstract::1. Salt intake is not only known to play an important role in determining blood pressure (BP) but has been shown to have other deleterious effects independent of BP. 2. Epidemiological and animal studies have provided evidence that salt intake may have an adverse effect on stroke mortality independent of BP. 3. Signif...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb01976.x
更新日期:1995-03-01 00:00:00
abstract::Recently, the roles of gene polymorphisms in poor responsiveness to aspirin were extensively investigated, with conflicting results. Therefore, we performed this meta-analysis to better assess the relationship between candidate genetic variants and poor responsiveness to aspirin. Eligible articles were searched in Pub...
journal_title:Clinical and experimental pharmacology & physiology
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更新日期:2018-05-21 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13274
更新日期:2020-06-01 00:00:00
abstract::1. The vascular contractile effects of polymorphonuclear leucocytes (PMN) isolated from control rabbits and from rabbits made atherosclerotic by 1% cholesterol feeding for 8 weeks were examined. 2. Rings of control rabbit thoracic aorta with or without endothelium were mounted at 2 g tension in 10 mL organ baths and w...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02486.x
更新日期:1994-02-01 00:00:00
abstract::1. Adrenocorticotrophin (ACTH) administration to sheep produces a rapid adrenally dependent hypertension which is maximal after 3 days and associated with increased cardiac output (CO) and heart rate (HR), while calculated total peripheral resistance remains unchanged. 2. This study investigated the proposal that a ce...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01611.x
更新日期:1989-07-01 00:00:00
abstract::1. The present study compared the binding and functional characteristics of tachykinin NK2 receptors in human detrusor muscle with those in human colon circular muscle. 2. In radioligand binding studies, similar KD values were observed for tachykinin NK2 receptor radioligands [125I]-neurokinin (NK) A, [125I]-[Lys5,Tyr...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
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更新日期:2003-09-01 00:00:00
abstract::1. Ethamsylate (diethylammonium 2,5-dihydroxybenzene sulfonate, Dicynene), a systemic haemostatic agent with an unknown mechanism of action, was tested for anti-inflammatory activity using the carrageenan-induced rat paw oedema test. 2. Ethamsylate was shown to be an effective anti-inflammatory agent with a time cours...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01285.x
更新日期:1990-12-01 00:00:00
abstract::1. The aim of the present study was to assess the protective effect of Sargassum polycystum (sulphated polysaccharide) extract against paracetamol-induced DNA strand breaks and modulation of membrane-bound phosphatases, protein thiols and inorganic cations during toxic hepatitis. 2. Seaweed extract (200 mg/kg per day ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04539.x
更新日期:2007-03-01 00:00:00
abstract::Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excre...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1985.tb02311.x
更新日期:1985-03-01 00:00:00
abstract::1. Mechanisms involved in the plasma extravasation observed following thermal injury of rat dorsal skin were investigated. 2. Heat applied to the dorsal skin of anaesthetized rats by a temperature-controlled skin heater (1 cm diameter) for 5 min induced temperature-dependent plasma protein extravasation at 48-48.5 deg...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb02705.x
更新日期:1997-11-01 00:00:00
abstract::Atherosclerosis is a complex chronic inflammatory disease that remains one of the leading causes of death and disability worldwide. A previous study reported that glaucocalyxin A (GLA), a natural ent-Kaurane diterpenoid triptolide, exhibits anti-atherosclerotic activity. However, the underlying molecular mechanism has...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13253
更新日期:2020-05-01 00:00:00
abstract::1. In a number of species, high concentrations of angiotensin II (AngII) receptors have been found in the rostral ventrolateral medulla (RVLM) in the hindbrain, which is an important region involved in the modulation of sympathetic vasomotor tone. The present review describes studies in which the contribution of angio...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb02820.x
更新日期:1996-09-01 00:00:00
abstract::We compared the intraocular pressure (IOP)-lowering effect and safety profile of latanoprost (Xalatan) with its generic variant, Glautan (Unipharm, Tel Aviv, Israel). After 1 and 4 weeks of treatment, a randomized, prospective, cross-over comparison was carried out that included patients with open-angle glaucoma or oc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/1440-1681.12329
更新日期:2015-02-01 00:00:00