Abstract:
:1 The reversible fatty acid amide hydrolase (FAAH) inhibitor OL135 reverses mechanical allodynia in the spinal nerve ligation (SNL) and mild thermal injury (MTI) models in the rat. The purpose of this study was to investigate the role of the cannabinoid and opioid systems in mediating this analgesic effect. 2 Elevated brain concentrations of anandamide (350 pmol g(-1) of tissue vs 60 pmol g(-1) in vehicle-treated controls) were found in brains of rats given OL135 (20 mg kg(-1)) i.p. 15 min prior to 20 mg kg(-1) i.p. anandamide. 3 Predosing rats with OL135 (2-60 mg kg(-1) i.p.) 30 min before administration of an irreversible FAAH inhibitor (URB597: 0.3 mg kg(-1) intracardiac) was found to protect brain FAAH from irreversible inactivation. The level of enzyme protection was correlated with the OL135 concentrations in the same brains. 4 OL135 (100 mg kg(-1) i.p.) reduced by 50% of the maximum possible efficacy (MPE) mechanical allodynia induced by MTI in FAAH(+/+)mice (von Frey filament measurement) 30 min after dosing, but was without effect in FAAH(-/-) mice. 5 OL135 given i.p. resulted in a dose-responsive reversal of mechanical allodynia in both MTI and SNL models in the rat with an ED(50) between 6 and 9 mg kg(-1). The plasma concentration at the ED(50) in both models was 0.7 microM (240 ng ml(-1)). 6 In the rat SNL model, coadministration of the selective CB(2) receptor antagonist SR144528 (5 mg kg(-1) i.p.), with 20 mg kg(-1) OL135 blocked the OL135-induced reversal of mechanical allodynia, but the selective CB(1) antagonist SR141716A (5 mg kg(-1) i.p.) was without effect. 7 In the rat MTI model neither SR141716A or SR144528 (both at 5 mg kg(-1) i.p.), or a combination of both antagonists coadministered with OL135 (20 mg kg(-1)) blocked reversal of mechanical allodynia assessed 30 min after dosing. 8 In both the MTI model and SNL models in rats, naloxone (1 mg kg(-1), i.p. 30 min after OL135) reversed the analgesia (to 15% of control levels in the MTI model, to zero in the SNL) produced by OL135.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Chang L,Luo L,Palmer JA,Sutton S,Wilson SJ,Barbier AJ,Breitenbucher JG,Chaplan SR,Webb Mdoi
10.1038/sj.bjp.0706699subject
Has Abstractpub_date
2006-05-01 00:00:00pages
102-13issue
1eissn
0007-1188issn
1476-5381pii
0706699journal_volume
148pub_type
杂志文章abstract::Authentic nitric oxide (NO; 0.1 - 10 micromoles) caused transient, dose-dependent relaxation of phenylephrine-induced tone without changing membrane potential in mesenteric arteries. Larger doses, above 10 micromoles, did not evoke more relaxation (maximal relaxation to 150 micromoles NO in denuded arteries, 69+/-7%, ...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0704127
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abstract::1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM) produ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12754.x
更新日期:1992-10-01 00:00:00
abstract::1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wist...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1989.tb11932.x
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abstract::1. Plasma, peripheral and thoracic lymph concentrations of penicillin V, phenethicillin, carbenicillin, ampicillin, cloxacillin, penicillin G, chloramphenicol and sulphadiazine were determined at various time intervals up to 6 h following intramuscular administration of 50 mg/kg to dogs.2. Peak plasma concentrations o...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1970.tb12906.x
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abstract:BACKGROUND AND PURPOSE:It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) ad...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2009.00597.x
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abstract::Perivascular adipose tissue (PVAT) is now recognized as an active player in vascular homeostasis. The expansion of PVAT in obesity and its possible role in vascular dysfunction have attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediat...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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doi:10.1038/sj.bjp.0704694
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abstract::Osteoarthritis (OA) is the most common disease of joints, which are complex organs where cartilage, bone and synovium cooperate to allow a range of movements. During progression of the disease, the function of all three main components is jeopardized. Nevertheless, the involvement of each tissue in OA development is s...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1994.tb13197.x
更新日期:1994-08-01 00:00:00
abstract::(1) We determined the effects of long-term treatment with aminoguanidine (AG), an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in aged Fisher 344 rats, using the aortic impedance analysis. (2) Normotensive rats were treated from 18 to 24 months with AG (1 g/l-1 in d...
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更新日期:2001-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb10306.x
更新日期:1988-03-01 00:00:00
abstract::1. The ability of the nitric oxide (NO)-releasing aspirin, NCX 4016, to control vasoconstrictor responses induced by electrical field stimulation (TNS) or by exogenous norepinephrine (NE) was investigated in perfused rat tail artery with intact endothelium. 2. NCX 4016 (25, 50 and 100 microM) dose-dependently antagoni...
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doi:10.1038/sj.bjp.0704869
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doi:10.1038/sj.bjp.0701602
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更新日期:1993-08-01 00:00:00
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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doi:
更新日期:1979-05-01 00:00:00
abstract::1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of chol...
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