Abstract:
:1. The possible roles of endothelial and smooth muscle cell hyperpolarization and nitric oxide (NO) in endothelium-dependent relaxation were examined in isolated rings of pig right coronary artery. 2. The effects of hyperpolarization were prevented with high K+ (30-125 mM), isotonic Krebs solutions. Functional antagonism due to high K(+)-induced smooth muscle contraction was prevented with 0.3 microM nifedipine (in all treatments, for consistency). All rings were contracted with the thromboxane-mimetic U46619, (1-100 nM) to bring them to an initial active force of within 30-50% of maximum contraction. 3. High K+ had no effects on the sensitivity (EC50) or time course of endothelium-dependent (substance P, SP; bradykinin, BK; calcimycin, A23187) and -independent (sodium nitroprusside, SNP) agents. Maximum relaxations (Rmax) to SP, BK and A23187 were reduced significantly by approximately 20% but only with 125 mM K+. 4. In normal K+ Krebs solution (5.9 mM), NG-nitro-L-arginine (L-NOARG; 100 microM) caused 40%, 20% and no reduction in Rmax for SP, BK and SNP respectively. EC50s for SP and BK were decreased significantly by approximately two fold whereas that for SNP was increased significantly by approximately ten fold. At all high K+ concentrations (30-125 mM), L-NOARG (100 microM) caused complete inhibition of relaxations to SP and BK but those to SNP were unaffected. 5. High K+ (30 mM) unmasked potent and concentration-dependent inhibition of relaxations of SP by L-NOARG. At 10 microM L-NOARG, all relaxation responses to SP were abolished and at the higher concentrations of SP (1-10 nM) small but significant contractions were observed. 6. N0-monomethyl-L-arginine (L-NMMA) had similar effects on relaxations to SP in the presence of 30 mM K+ except that maximum inhibition (40%) of Rmax was achieved at 10 MicroM L-NMMA and this was not increased with either 100 or 1000 MicroM L-NMMA. In normal K+, L-NMMA (1000 MicroM) only decreased the EC50 by approximately two fold, without affecting Rmax.7. High choline+ (25, 75 and 125 mM) isotonic Krebs also had no direct effect on the relaxations to SP,but like high K+, enabled L-NOARG (100 MicroM) to inhibit these responses completely. Neither charybdotoxin(30 nM) nor substitution of 25 mM NaCl with 50 mM sucrose had any direct effect on relaxations to SP or on the block of relaxations to SP by L-NOARG (100 MicroM).8. In conclusion, most if not all of the endothelium-dependent relaxation in the pig coronary artery in vitro is due to NO, but hyperpolarization can supplement 60% -80% of this response if NO synthesis is blocked. Multiple endothelium-derived factors could not only explain heterogeneity of the degree of block of endothelium-dependent relaxation responses by L-arginine analogues, but also constitute important 'back-up' mechanisms for control of arterial diameter.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kilpatrick EV,Cocks TMdoi
10.1111/j.1476-5381.1994.tb13110.xsubject
Has Abstractpub_date
1994-06-01 00:00:00pages
557-65issue
2eissn
0007-1188issn
1476-5381journal_volume
112pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01391.x
更新日期:2011-09-01 00:00:00
abstract::1 The effect of phenoxybenzamine on the efflux of [3H]-noradrenaline and the mechanical response to single pulse excitation of superfused guinea-pig vas deferens was determined to examine the validity of the currently accepted hypothesis of a presynaptic negative feedback system on adrenergic nerve terminals. 2 The ad...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb13686.x
更新日期:1979-06-01 00:00:00
abstract::1. Heterologous desensitization or intermolecular cross-talk plays a critical role in regulating intracellular signalling by diverse members of the G-protein-coupled receptor superfamily. We have previously established that the alpha and beta isoforms of the human thromboxane A(2) receptor (TP) undergo differential de...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705695
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Rosiglitazone is an anti-diabetic drug improving insulin sensitivity and glucose uptake in skeletal muscle and adipose tissues. However, several recent clinical trials suggest that rosiglitazone can increase the risk of cardiovascular ischaemia, although other studies failed to show such risks. T...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01539.x
更新日期:2011-12-01 00:00:00
abstract::Nociceptive tail flick latencies (TFL) were recorded in response to noxious thermal stimuli applied to lightly anaesthetized rats. The effects of intrathecally administered dopamine receptor agonists alone and combined with dopamine receptor antagonists were examined upon the TFL. Experiments were repeated on animals ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb16820.x
更新日期:1987-01-01 00:00:00
abstract::1. Impairment of nitric oxide (NO)/cyclic GMP production and/or increased activities of thromboxane A2 (TXA2) and endothelin-1 (ET-1) have been associated with pulmonary hypertension. We have analysed the interactions of noradrenaline (NA), the TXA2-mimetic U46619 and ET-1 with the relaxation induced via cyclic GMP in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701257
更新日期:1997-08-01 00:00:00
abstract::1 The effects of gamma-aminobutyric acid (GABA) and related substances were examined in guinea-pig ileum longitudinal muscle.2 GABA at doses ranging from 10(-7) M to 3 x 10(-6) M elicited a relaxation while at higher doses (3 x 10(-6) M - 10(-4) M), as previously described, it caused a contraction followed by relaxati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb08807.x
更新日期:1983-03-01 00:00:00
abstract::1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice. We also studied a negative inotropic effect of (-)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704700
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentrat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12194
更新日期:2013-07-01 00:00:00
abstract::1. The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ;chemosensitive zones' situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08532.x
更新日期:1973-12-01 00:00:00
abstract::The intravenous administration of naloxone 2 min before coronary artery occlusion in anaesthetized dogs reduced the incidence and severity of cardiac arrhythmias during coronary occlusion (20 min) and reperfusion (120 min) in a dose-related manner. It also reduced the mortality. At a dose of 1 mg kg-1 (the maximum dos...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10186.x
更新日期:1986-03-01 00:00:00
abstract::1. A method is presented which enables the dissociation constant (KI) of a competitive, pseudo-irreversible or non-competitive antagonist-receptor complex to be estimated without knowledge of agonist concentrations. 2. The technique has been tested using sets of concentration-response data which simulated these variou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14047.x
更新日期:1994-01-01 00:00:00
abstract::1. The effects of the nonpeptide angiotensin II receptor (AT) antagonists losartan and PD 123319 on actions of angiotensin II in the rat caudal artery and rat vas deferens preparations were investigated. 2. Angiotensin II (1.0 microM) increased perfusion pressure in isolated segments of the rat caudal artery. This inc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13313.x
更新日期:1995-03-01 00:00:00
abstract::1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 2 In i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14272.x
更新日期:1992-02-01 00:00:00
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
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb12906.x
更新日期:1970-06-01 00:00:00
abstract::Chronic heart failure (HF) is characterized by left ventricular (LV) structural remodeling, impaired function, increased circulating noradrenaline (NA) levels and impaired responsiveness of the myocardial beta-adrenoceptor (betaAR)-adenylyl cyclase (AC) system. In failing hearts, inhibition of the sodium/proton-exchan...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706714
更新日期:2006-05-01 00:00:00
abstract::1. The regulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels by cholinoceptors has been studied in cultured bovine adrenal medullary cells. 2. Acetylcholine (100 microM), nicotine (10 microM) and dimethylphenylpiperazinium (20 microM) each increased cellular cyclic AMP levels 2 to 4 fold over 5 min in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14341.x
更新日期:1992-06-01 00:00:00
abstract::Since protease-activated receptors (PARs) are distributed throughout the gastrointestinal tract, we investigated the role of PARs in modulation of the motility of the rat oesophageal muscularis mucosae. Thrombin produced contraction of segments of the upper and lower part of the smooth muscle. Trypsin contracted both ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703590
更新日期:2000-10-01 00:00:00
abstract::1. Pharmacological inhibitors of protein kinase A (PKA) and protein phosphatases 1/2A were used to determine whether basal L-type Ca(2+) current (I(Ca)) observed in the absence of exogenous beta-adrenergic receptor stimulation is sustained by PKA-mediated phosphorylation. Amphotericin B was used to record whole-cell I...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706809
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) metabolizes compounds containing catechol structures and has two forms: soluble (S-COMT) and membrane-bound (MB-COMT). Here we report the generation of a mouse line that expresses MB-COMT but not S-COMT. We compared the effects of deleting S-COMT only or both C...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00494.x
更新日期:2009-12-01 00:00:00
abstract::1. We have investigated an aspect of the regulation of cortical pyramidal neurone activity. Microdialysis was used to assess whether topical application of drugs (in 10 microliter) to fill a burr hole over the frontal cortex, where part of the corticostriatal pathway originates, would change concentrations of the exci...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15020.x
更新日期:1995-08-01 00:00:00
abstract::1. Phenylarsine oxide (PAO) is commonly used to inhibit tyrosine phosphatase activity. However, PAO can affect a variety of different processes because of its ability to promote sulfhydryl oxidation. In the present study, we investigated the effects that PAO has on basal and beta-adrenergically stimulated L-type Ca(2+...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705845
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Central anti-nociceptive actions of baclofen involve activation of K+ channels. Here we assessed what types of K+ channel might participate in the peripheral anti-nociception induced by baclofen. EXPERIMENTAL APPROACH:Nociceptive thresholds to mechanical stimulation in rat paws treated with intr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706898
更新日期:2006-11-01 00:00:00
abstract::1. Yawning was induced by subcutaneous (s.c.) injection of low doses of apomorphine to rats. This effect decreased with increasing doses of the drug. 2. Intraperitoneal (i.p.) pretreatment of animals with sulpiride (D2-receptor blocker) reduced the frequency of the yawns induced by apomorphine, while SCH 23390 (D1-rec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11893.x
更新日期:1989-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Saponins isolated from Panax notoginseng (Burk.) F.H. Chen have been shown to relieve thrombogenesis and facilitate haemostasis. However, it is not known which saponin accounts for this haemostatic effect. Hence, in the present study we aimed to identify which saponins contribute to its haemostat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12435
更新日期:2014-01-01 00:00:00
abstract:BACKGROUNDS AND PURPOSE:Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.01853.x
更新日期:2012-06-01 00:00:00
abstract::1. Daily i.p. administration, for eight days, of the cholinesterase inhibitor disulfoton to rats produced mild to moderate signs of intoxication (tremors, incontinence and diarrhoea) but no deaths.2. Segments of ileum taken from the treated rats were subsensitive to carbachol but the vas deferens and the uterus did no...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08350.x
更新日期:1973-07-01 00:00:00
abstract::1. Tyrosine kinases have been proposed as regulators of voltage-operated calcium channels. The effects of a range of structurally different inhibitors of protein tyrosine kinases (PTK) were examined on voltage-operated calcium channel currents (I(Ba)) and pp60(c-src) kinase (c-src) activity in vitro. 2. I(Ba) was meas...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703186
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14164
更新日期:2018-05-01 00:00:00
abstract::1. An antisense approach to block nitric oxide (NO) synthesis was developed, complementing the widely used chemical inhibitors and overcoming problems associated with their use in studying the roles of NO. 2. Murine macrophage cell lines (J774.2) were generated expressing a 500 bp sequence from inducible NO synthase (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0700863
更新日期:1997-01-01 00:00:00