Abstract:
:1. The effect of the myorelaxant drugs baclofen, diazepam and tizanidine have been compared on in vitro preparations of baby rat spinal cord and adult rat superior cervical ganglion. 2. Dorsal root-elicited long duration (time to half decay 9.71 +/- 0.29 s.e. mean, n = 31) ipsilateral ventral root reflexes (DR-VRP), measured as integrated area, of immature rat spinal cord preparations were abolished by RS-2-amino-5-phosphonopentanoate (AP5) (EC50 8.13 +/- 0.92 microM, n = 3). The initial short latency component of DR-VRP was resistant to AP5. 3. Baclofen abolished both components of the DR-VRP. Respective EC50 values for the AP5-insensitive and AP5-sensitive components were 237 +/- 68 nM (n +/- 7) and 57 +/- 10 nM (n = 7). These effects of baclofen were reversed by the GABAB antagonist, CGP35348. The apparent Kd values (16.7 +/- 6.4 microM, n = 3 and 14.3 +/- 3.9 microM, n = 6 respectively) for this reversal were not significantly different. 4. Tizanidine, clonidine and diazepam had no effect on the AP5-insensitive component of the DR-VRP. 5. The AP5-sensitive long duration component of the DR-VRP was depressed to respective maximal levels of 23.2 +/- 1.4% (n = 7), 18.8 +/- 3.8% (n = 4) and 47.6 +/- 1.6% (n = 5) of control (100%) levels by tizanidine (EC50 135 +/- 33 nM), clonidine (EC50 26.0 +/- 2.2 nM) and diazepam (EC25 114 +/- 12 nM, n = 4). The depressant effects of tizanidine and clonidine were reversed by idazoxan (1 microM). Flumazenil (I microM) failed to reverse the depressant effect of tizanidine. The depressant effect of diazepam was reversed by flumazenil (1 microM) but not by idazoxan (1 microM). Naloxone 1 M did not reverse the effects of either tizanidine or diazepam.6. In the presence of tetrodotoxin (0.1 SAM) which abolished synaptic activity, clonidine, tizanidine or diazepam (10, 100 and 101JM respectively) produced no significant antagonism of NMDA-induced depolarizations recorded from ventral roots.7. Control (100%) synaptic responses of rat superior cervical ganglion preparations were depressed respectively to near maximal levels of 60.0 +/- 5.2% (n = 4) and 60.7 +/- 5.6% (n = 5) by clonidine (0.5 JAM,EC25 15.3 +/- 3.0 nM) and tizanidine (1 JAM, EC25 227 +/- 83 nM). These depressant effects were reversed by idazoxan (1 AM). Baclofen (EC25 28.7 +/- 10.0, n = 3) depressed the postganglionic response to a maximum level of 71.8 + 2.4% (n = 4) control at a concentration of 100 microM. The latter depressant action was reversed by the GABAB receptor antagonist, CGP35348 (1 mM). Diazepam (1 microM) had no significant effect on ganglionic transmission.8. It is concluded that the activation of benzodiazepine or M2-noradrenaline receptors can modulate NMDA receptor-mediated excitatory synaptic pathways whereas synaptic excitation from primary afferent terminals, mediated by non-NMDA receptors, appears to lack the propensity for this type of modulation. The results show also that the isolated spinal preparation can be used to identify central myorelaxant actions that are mediated through functional benzodiazepine or X2-noradrenaline receptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Siarey RJ,Long SK,Evans RHdoi
10.1111/j.1476-5381.1992.tb12794.xsubject
Has Abstractpub_date
1992-10-01 00:00:00pages
628-33issue
2eissn
0007-1188issn
1476-5381journal_volume
107pub_type
杂志文章abstract::1. The role of both exogenously administered and endogenously generated bradykinin (BK) on LPS-induced eosinophil accumulation in the mice pleural cavity was investigated by means of treatment with BK selective receptor agonists/antagonists and captopril. 2. Intrathoracic (i.t.) injection of LPS (250 ng cavity(-1)) in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702567
更新日期:1999-05-01 00:00:00
abstract::Arthritis-associated inflammatory pain represents a serious medical problem worldwide. Current treatments for arthritic pain are not very effective and cause unwanted side effects. Resolvins, including the resolvin D and resolvin E series, are a family of novel endogenous lipid mediators derived from ω-3 polyunsaturat...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2011.01348.x
更新日期:2011-09-01 00:00:00
abstract::1. Pregnancy is characterized by a decrease in systemic vascular resistance and a blunting of the angiotensin II (AII) pressor response. We studied the role of nitric oxide (NO) and prostanoids in these vascular changes of pregnancy in anaesthesized, ganglion blocked non-pregnant and pregnant rats. 2. Inhibition of NO...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1995.tb13297.x
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The use of tubulin-binding compounds, which act in part by inhibiting tumour angiogenesis, has become an integral strategy of tumour therapy. Recently, tubulysins were identified as a novel class of natural compounds of myxobacterial origin, which inhibit tubulin polymerization. As these compound...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2012.02037.x
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abstract::1. The inflammatory response induced by poly-L-arginine in the rat hind-paw was studied both by measuring paw oedema and histologically. 2. The paw volume was measured with a hydroplethysmometer at 0.5, 1, 2, 4, 6 and 18 h after the subplantar injection of the polycation. Protein extravasation was evaluated with Evans...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14193.x
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied. EXPERIMENTAL APPROACH:Microdial...
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doi:10.1111/j.1476-5381.2009.00242.x
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abstract::1. The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A (NKA), [beta-Ala8]NKA (4-10) and [MePhe7]neurokinin B (NKB) at T13 thoracic spinal cord level were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP 67580), ...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0701223
更新日期:1997-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10735.x
更新日期:1984-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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abstract:BACKGROUND AND PURPOSE:Arachidonyl trifluoromethyl ketone (ATK) is widely used as an inhibitor of cytosolic group IV phospholipase A(2) (cPLA(2)) and calcium-independent group VI phospholipase A(2) (iPLA(2)). ATK thus reduces arachidonic acid (AA) substrate for cyclooxygenase (COX; also known as prostaglandin H synthas...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0705614
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally i...
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更新日期:2000-02-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1977.tb07554.x
更新日期:1977-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2019-05-14 00:00:00
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更新日期:2002-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07881.x
更新日期:1979-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13110.x
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abstract:BACKGROUND AND PURPOSE:Pancreatic cancer is a solid tumour that is often fatal. Hence, there is an urgent need to identify new drug targets for this disease. Highly proliferating cancer cells have an increased demand for nutrients and, therefore, need to up-regulate selective amino acid transporters. Here, we investiga...
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12771.x
更新日期:1992-10-01 00:00:00
abstract::NO is a neurotransmitter released from enteric inhibitory neurons and responsible for modulating gastrointestinal (GI) motor behaviour. Enteric neurons express nNOS (NOS1) that associates with membranes of nerve varicosities. NO released from neurons binds to soluble guanylate cyclase in post-junctional cells to gener...
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1993-12-01 00:00:00
abstract::1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14940.x
更新日期:1995-04-01 00:00:00
abstract::1. In this study we examined the effects of cortistatin, a putative endogenous ligand for somatostatin (SRIF) receptors, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, by use of intracellular and whole cell patch clamp recording. We have compared the actions of cortistatin with those of SRIF...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701541
更新日期:1997-12-01 00:00:00
abstract::Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused o...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01711.x
更新日期:2012-04-01 00:00:00