Abstract:
:1 The present study examined effects of agonist enzymes and receptor-activating peptides for protease-activated receptors (PARs) on duodenal motility in the rat, and also investigated possible mechanisms underlying the evoked responses. 2 Thrombin at 0.03-0.1 microM and the PAR-1-activating peptide SFLLR-NH2 at 3-100 microM or TFLLR-NH2 at 10-50 microM produced a dual action, relaxation followed by contraction of the duodenal longitudinal muscle. The PAR-2-activating peptide SLIGRL-NH2 at 10-100 microM elicited only small contraction. Trypsin at 0.08 microM induced small contraction, or relaxation followed by contraction, depending on preparations. The PAR-4-activating peptide GYPGKF-NH2 at 1000 microM exhibited no effect. 3 The contractile responses of the duodenal strips to TFLLR-NH2 and to SLIGRL-NH2 were partially attenuated by the L-type calcium channel blocker nifedipine (1 microM), the protein kinase C inhibitor GF109203X (1 microM) and the tyrosine kinase inhibitor genistein (15 microM), but were resistant to indomethacin (3 microM) and tetrodotoxin (1-10 microM). 4 The relaxation of the preparations exerted by TFLLR-NH2 was unaffected by indomethacin (3 microM), propranolol (5 microM), NG-nitro-L-arginine methyl ester (100 microM) and tetrodotoxin (1-10 microM). This relaxation was resistant to either GF109203X (1 microM) or genistein (15 microM), but was, remarkably, attenuated by combined application of these two kinase inhibitors. 5 Apamin (0.1 microM), an inhibitor of calcium-activated, small-conductance potassium channels, but not charybdotoxin (0.1 microM), completely abolished the PAR-1-mediated duodenal relaxation, and significantly enhanced the PAR-1-mediated contraction. 6 These findings demonstrate that PAR-1 plays a dual role, suppression and facilitation of smooth muscle motility in the rat duodenum, while PAR-2 plays a minor excitatory role in the muscle, and that PAR-4 is not involved in the duodenal tension modulation. The results also suggest that the contractile responses to PAR-1 and PAR-2 activation are mediated, in part, by activation of L-type calcium channels, protein kinase C and tyrosine kinase, and that the relaxation response to PAR-1 activation occurs via activation of apamin-sensitive, but charybdotoxin-insensitive, potassium channels, in which both protein kinase C and tyrosine kinase might be involved synergistically.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kawabata A,Kuroda R,Nishikawa H,Kawai Kdoi
10.1038/sj.bjp.0702755subject
Has Abstractpub_date
1999-10-01 00:00:00pages
865-72issue
4eissn
0007-1188issn
1476-5381journal_volume
128pub_type
杂志文章abstract::1 The effect of intrarenal histamine, dimaprit (H2-agonist) and 2-(2-pyridyl) ethylamine (H1-agonist) on renin release was examined in anaesthetized dogs. 2 In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no chang...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10495.x
更新日期:1983-05-01 00:00:00
abstract::1. Using a guinea-pig model of allergic asthma, we investigated the role of L-arginine limitation in the allergen-induced deficiency of nitric oxide (NO) and airway hyperreactivity (AHR) after the early asthmatic reaction, by examining the effects of various concentrations of the NO synthase (NOS) substrate on the res...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702882
更新日期:1999-11-01 00:00:00
abstract::Allergic inflammatory responses contribute to the symptoms of a number of diseases including atopic dermatitis, asthma and rhinitis. Cationic proteins are released from inflammatory cells and levels are known to be raised in disease states. Using an in vivo model of acute inflammation, we investigated the characterist...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704172
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In the ciliary muscle, the tonic component of the contraction produced by cholinergic agonists is highly dependent on Ca2+ provided by influx through non-selective cation channels (NSCCs) opened by stimulation of M3 muscarinic receptors. We examined effects of YM-254890 (YM), a Gq/11-specific inh...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.140
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01179.x
更新日期:2011-04-01 00:00:00
abstract::1. Leptin, a pleiotropic hormone believed to regulate body weight, has recently been associated with inflammatory states and immune activity. Here we have studied the effect of leptin on expression of IFN-gamma-induced nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2), both prominent markers of macrophage act...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704903
更新日期:2002-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:7-Ketocholesterol, an oxysterol present in atherosclerotic lesions, induces smooth muscle cell (SMC) death, thereby destabilizing plaques. Statins protect patients from myocardial infarction, though they induce SMC apoptosis. We investigated whether statins and 7-ketocholesterol exerted additive ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.181
更新日期:2008-07-01 00:00:00
abstract::1. In isolated Langendorff-perfused, electrically-paced, hearts of guinea-pigs, global low-flow-ischaemia (LFI; at 0.7 ml min-1) resulted in marked increases in the rates of release of lactate, lactate dehydrogenase (LDH) and creatine kinase (CK) over a 30 min period. At the end of the LFI period, tissue ATP content w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13637.x
更新日期:1993-07-01 00:00:00
abstract::1. We studied the lactotroph cells of the rat by both in vivo and in vitro pharmacological techniques for the presence of D1-receptors. Both approaches revealed the presence of D2-receptor, stimulated by quinpirole (resulting in an inhibition of prolactin secretion) and blocked by domperidone. 2. Administration of fen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12354.x
更新日期:1991-08-01 00:00:00
abstract::1. This study sets out to examine the effect of rilmenidine administered systemically on basal and reflexly activated renal nerve activity in Wistar and stroke prone spontaneously hypertensive rats (SHRSP). 2. Animals were anaesthetized with chloralose/urethane, stimulating electrodes were placed on the brachial plexi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16029.x
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In endothelial dysfunction, signalling by nitric oxide (NO) is impaired because of the oxidation and subsequent loss of the soluble guanylyl cyclase (sGC) haem. The sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino)methyl[benzoic]acid (BAY 58-2667) is a haem-mimetic abl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00263.x
更新日期:2009-07-01 00:00:00
abstract::1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15198.x
更新日期:1996-01-01 00:00:00
abstract::Cyclic adenosine 3',5'-monophosphage (cyclic AMP) levels in guinea-pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo-bronchial relaxant action of VIP may be mediated by stimulation of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08471.x
更新日期:1978-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates insulin biosynthesis and secretion in a glucose-dependent manner and has been reported to induce vasodilatation. Here, we examined the possible vasorelaxant effect of GLP-1 and its underlying mechanisms. EXPERIMENTAL APPROACH:...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14534
更新日期:2019-02-01 00:00:00
abstract::1. The effect on membrane currents of infection of mouse neuroblastoma NA cells with rabies virus was studied by using the whole-cell patch clamp technique. 2. Three types of membrane currents, namely voltage-dependent Na+ current (I(Na)), delayed rectifier K+ current (I(K-DR)) and inward rectifier K+ current (I(K-IR)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702473
更新日期:1999-04-01 00:00:00
abstract::1. Many apparent actions of adenosine 5'-triphosphate (ATP) are mediated by adenosine produced by enzymatic hydrolysis of the nucleotide. Previously described actions of ATP in the CNS have been partly due to this phenomenon. In the present study analogues of ATP, which are not hydrolysed to adenosine, were used to se...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11996.x
更新日期:1989-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In small arteries, small conductance Ca²⁺-activated K⁺ channels (SK(Ca)) and intermediate conductance Ca²⁺-activated K⁺ channels (IK(Ca)) restricted to the vascular endothelium generate hyperpolarization that underpins the NO- and PGI₂-independent, endothelium-derived hyperpolarizing factor respo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12160
更新日期:2013-06-01 00:00:00
abstract::1. Propranolol, a beta-adrenoceptor blocking drug with local anaesthetic and a direct myocardial depressant action, and MJ 1999, a beta-adrenoceptor blocking drug which has no local anaesthetic or intrinsic sympathomimetic action, were compared for beta-adrenoceptor blocking activity in man.2. Propranolol was 2.67 tim...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1476-5381.1970.tb10596.x
更新日期:1970-05-01 00:00:00
abstract::The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0705750
更新日期:2004-04-01 00:00:00
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...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13616
更新日期:2016-12-01 00:00:00
abstract::1. CS-747 is a novel thienopyridine-type platelet ADP inhibitor which lacks in vitro activity. This study examined pharmacological profiles of R-99224, a hepatic metabolite of CS-747. 2. R-99224 produced a concentration-dependent inhibition of in vitro platelet aggregation in washed human platelets (0.03 - 1 microg ml...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703761
更新日期:2001-01-01 00:00:00
abstract::1. Experiments were designed to determine whether endothelium-dependent relaxing factor(s) released by acetylcholine from the canine femoral artery influences the membrane potential of coronary arterial smooth muscle. 2. The membrane potential was recorded in small canine coronary arteries (internal diameter less than...
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::We have studied the recovery of receptor binding and of isoprenaline-stimulated cyclic AMP responses after chronic (2-5 days) exposure of tissue-cultured living rat heart cells to several beta-adrenoceptor antagonists. Most experiments were performed with [3H]- (+/-)-carazolol and [3H]-(+/-)-CGP 12177, as prototypes o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10814.x
更新日期:1984-07-01 00:00:00
abstract::1. Interactions of bath-applied pentobarbitone and gamma-aminobutyric acid (GABA) on neurones in isolated superior cervical ganglia of the rat have been examined with intracellular microelectrodes. 2. Pentobarbitone itself (30 micrometer-1 mM) showed no clear or consistent GABA-like effects: changes in resting input c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07791.x
更新日期:1978-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Diabetes mellitus is associated with a specific cardiomyopathy. We compared the cardioprotective effects of an endothelin-A receptor blocker (ET(A)-RB) with those of an angiotensin-converting enzyme inhibitor (ACE-I) in rats with streptozotocin (STZ)-induced diabetes. EXPERIMENTAL APPROACH:Diabe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707325
更新日期:2007-08-01 00:00:00
abstract::1 Acetylcholine-induced contractions of the isolated chronically denervated soleus muscle of the mouse consist of two phases, but both phases are equivalent to the contracture phase seen in vivo.2 Low [Ca(2+)](0) (0.5-1.5 mM) augmented peak tension, as well as the rate of relaxation, of the first phase, but inhibited ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07556.x
更新日期:1977-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)gamma activation reduces inflammation and atherosclerosis, expression of PPARgamma in cells and its modulation by smoking are poorly investigated. We previou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00442.x
更新日期:2009-11-01 00:00:00
abstract:UNLABELLED:Midkine (MK) is a heparin-binding growth factor or cytokine and forms a small protein family, the other member of which is pleiotrophin. MK enhances survival, migration, cytokine expression, differentiation and other activities of target cells. MK is involved in various physiological processes, such as devel...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12353
更新日期:2014-02-01 00:00:00
abstract::It was confirmed that morphine administration in vivo produced a selective decrease in the calcium content of synaptosomal fractions prepared from rat cerebral cortices. This effect was prevented by naloxone. 2 After morphine or naloxone, there were no changes in the sodium, potassium and magnesium contents of any of ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb10379.x
更新日期:1976-08-01 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...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707432
更新日期:2007-12-01 00:00:00