Abstract:
:1 Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA, which are caused by reactive oxygen species (ROS). Here we investigate the effects of the PARS inhibitors 3-aminobenzamide (3-AB), nicotinamide and 1,5-dihydroxyisoquinoline (ISO) on the circulatory failure and the organ injury/dysfunction caused by haemorrhage and resuscitation in the anaesthetized rat. 2 Haemorrhage (sufficient to lower mean arterial blood pressure to 50 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure to 66+/-4 mmHg (control, n=13). This circulatory failure was not affected by administration (5 min prior to resuscitation) of 3-AB (10 mg kg-1 i.v., n=7), nicotinamide (10 mg kg-1 i.v., n=6) or ISO (3 mg kg-1 i.v., n=6). 3 Haemorrhage and resuscitation also resulted in rises in the serum levels of urea and creatinine. This renal dysfunction was attenuated by 3-AB and nicotinamide, but not by nicotinic acid (n=7), an inactive analogue of nicotinamide. Although ISO (n=6) also attenuated the renal dysfunction caused by haemorrhage and resuscitation, its vehicle (10% DMSO, n=4) had the same effect. 4 Haemorrhagic shock resulted in enhanced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipase, indicating the development of hepatocellular and pancreatic injury, respectively. Similarly, haemorrhagic shock also resulted in an increase in the serum levels of creatine kinase (CK) indicating the development of neuromuscular injury. This was attenuated by 3-AB and nicotinamide, but not by nicotinic acid. Although ISO also attenuated the liver, pancreatic and neuromuscular injury caused by haemorrhagic shock, its vehicle had the same effect. 5 Thus, activation of PARS contributes to the organ injury and dysfunction caused by haemorrhage and resuscitation in the rat.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
McDonald MC,Filipe HM,Thiemermann Cdoi
10.1038/sj.bjp.0702928subject
Has Abstractpub_date
1999-11-01 00:00:00pages
1339-45issue
6eissn
0007-1188issn
1476-5381journal_volume
128pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:The anti-cancer agent [Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (SP-G) modulates gastrin releasing peptide (GRP) and arginine vasopressin signalling in small cell lung cancer cells leading to growth arrest and apoptosis. We have shown that SP-G acts as a biased agonist at GRP receptors...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2008.00003.x
更新日期:2009-01-01 00:00:00
abstract::1 The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of gamma-aminobutyric acid (GABA) and D-aspartate by rat thalamic slices has been investigated. 2 A high, supra-anaesthetic concentration of methohexitone increased the uptake of both D-aspartate and GABA. 3 None of the anaesth...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1982.tb08776.x
更新日期:1982-01-01 00:00:00
abstract::Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new a...
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abstract:BACKGROUND AND PURPOSE:Pemphigus and pemphigoid diseases are characterized and caused predominantly by IgG autoantibodies targeting structural proteins of the skin. Their current treatment relies on general and prolonged immunosuppression that causes severe adverse events, including death. Hence, novel safe and more ef...
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abstract::1. Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus muscle from 8-week streptozotocin-induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been inves...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1995.tb16348.x
更新日期:1995-06-01 00:00:00
abstract::The effect of bath-applied luteinizing hormone-releasing factor (LHRF) was recorded in voltage-clamped bullfrog lumbar sympathetic neurones. At a holding potential of -- 30 mV, LHRF induced a steady inward (depolarizing) current and reduced membrane conductance; at -- 60 mV LHRF produced negligible inward current and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb14547.x
更新日期:1980-03-01 00:00:00
abstract::1. Male rats treated with guanethidine 25 mg/kg daily for eight weeks had no demonstrable ejaculatory function immediately after cessation of treatment. Four weeks later, ejaculatory function had returned in two-thirds of the males, and after eight weeks, all males were able to deposit sperm in the vagina. However, fe...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1973.tb08219.x
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1982.tb08775.x
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journal_title:British journal of pharmacology
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更新日期:2009-12-01 00:00:00
abstract::1. The pharmacological characteristics of RP 67580, a non-peptide tachykinin NK1 receptor antagonist, and its effects on a reflex response evoked by stimulation of primary afferent fibres, were examined in isolated neonatal spinal cord preparations of the rat. Potentials were recorded extracellularly from a lumbar ven...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17116.x
更新日期:1994-12-01 00:00:00
abstract::1. In pithed rats, preganglionic vagal nerve stimulation (at 5 Hz) elicited a bradycardia. This bradycardia was potentiated by the angiotensin converting enzyme inhibitor, captopril (1 mg kg-1, i.v.) by about 40%. Subsequent angiotensin II infusion (0.03 micrograms kg-1 min-1) reversed this effect. A similar facilitat...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13807.x
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abstract::The concentration of intracellular free Ca2+ ( [Ca2+]i) in human blood platelets was measured by use of the fluorescent probe quin-2. 5-Hydroxytryptamine (5-HT) caused a rapid increase of [Ca2+]i in the presence or absence of Ca2+ in the medium. The [Ca2+]i-rise was less marked in the absence of Ca2+ and could be anta...
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doi:10.1111/j.1476-5381.1985.tb12939.x
更新日期:1985-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-05-01 00:00:00
abstract::1. In circular muscle strips of the fundus and corpus of guinea-pig stomach, mechanical responses to catecholamines were studied mainly in the presence of a prostaglandin biosynthesis inhibitor, meclofenamate. 2. Normal preparations developed considerable muscle tone, and adrenaline (10-100 microM) in the presence of ...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1990.tb14162.x
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Kyotorphin (KTP; L-Tyr-L-Arg), an endogenous neuropeptide, is potently analgesic when delivered directly to the central nervous system. Its weak analgesic effects after systemic administration have been explained by inability to cross the blood-brain barrier (BBB) and detract from the possible cl...
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pub_type: 杂志文章,随机对照试验
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更新日期:2014-04-01 00:00:00
abstract::In dog trachea in situ, perfused arterially with blood, isoprenaline, glyceryl trinitrate and N-nitroso-N-morpholinoamino-acetonitrile (SIN-1A) given intra-arterially, decreased tracheal tone which had been elevated by neostigmine and increased tracheal blood flow. Glyceryl trinitrate and SIN-1A were more effective on...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb16764.x
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abstract::1. The tachykinin receptor mediating contraction of the guinea-pig isolated proximal urethra has been characterized by use of receptor selective agonists and antagonists. All experiments were performed in the presence of peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each) in order to reduce peptide...
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更新日期:1992-08-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2008-05-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:1986-06-01 00:00:00
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更新日期:2002-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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journal_title:British journal of pharmacology
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更新日期:2011-11-01 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:2007-11-01 00:00:00
abstract::1. Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15661.x
更新日期:1996-08-01 00:00:00