Abstract:
:1. The effects of a series of nine GABAB receptor antagonists of widely varying potencies on electrically stimulated release from cortical slices of [3H]-GABA in the absence or presence of 10 microM of the GABAB agonist, (-)-baclofen and of endogenous glutamate in the presence of (-)-baclofen were compared. 2. The concentrations of the compounds half maximally increasing [3H]-GABA release (EC50's) at a stimulation frequency of 2 Hz correlated well with the IC50 values obtained from the inhibition of the binding of the agonist, [3H]-CGP 27492, to GABAB receptors in rat brain membranes (rank order of potency: CGP 56999 A > or = CGP 55845 A > CGP 52432 > or = CGP 56433 A > CGP 57034 A > CGP 57070 A > or = CGP 57976 > CGP 51176 > CGP 35348). 3. Likewise, the concentrations causing half-maximal increases of [3H]-GABA in the absence or presence of (-)-baclofen, and of endogenous glutamate in the presence of (-)-baclofen, correlated well with each other. Reports in the literature suggesting the CGP 35348 exhibits a 70 fold preference for inhibition of (-)-baclofen's effects on glutamate over [3H]-GABA release, and that CGP 52432 shows a 100 fold preference in the opposite sense, could not be confirmed in our model. 4. Therefore, our results suggest that, if there are pharmacological differences between GABAB autoreceptors and GABAB heteroreceptors on glutamatergic nerve endings in the rat cortex, they are not revealed by this series of compounds of widely different potencies. 5. In particular, our results with CGP 35348 and CGP 52432 do not support the hypothesis that GABAB autoreceptors and GABAB heteroreceptors on glutamatergic nerve endings represent subtypes with different pharmacology.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Waldmeier PC,Wicki P,Feldtrauer JJ,Mickel SJ,Bittiger H,Baumann PAdoi
10.1111/j.1476-5381.1994.tb17168.xsubject
Has Abstractpub_date
1994-12-01 00:00:00pages
1515-21issue
4eissn
0007-1188issn
1476-5381journal_volume
113pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:AZ11645373 and N-{2-methyl-5-[(1R, 5S)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-ylcarbonyl]phenyl}-2-tricyclo[3.3.1.13,7]dec-1-ylacetamide hydrochloride (compound-22) are recently described P2X(7) receptor antagonists. In this study we have further characterized these compounds to determine their mecha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00135.x
更新日期:2009-04-01 00:00:00
abstract::Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12159
更新日期:2013-06-01 00:00:00
abstract::1 Neuroprotection has been reported after either activation or blockade of the group I metabotropic glutamate receptor subtype 5 (mGluR5). However, some recent evidence suggests that protection provided by mGluR5 antagonists may reflect their ability to inhibit N-methyl-D-aspartate (NMDA) receptor activity. 2 Here, in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706219
更新日期:2005-06-01 00:00:00
abstract::1. Preparations were developed whereby the hypogastric ganglion of the rat or guinea-pig was perfused through its vasculature with saline solutions. Drugs were injected into the perfusion stream, and their effects were indicated by contractions of the vas deferens. The base of this organ could be ligated to prevent th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07286.x
更新日期:1972-03-01 00:00:00
abstract::The pharmaceutical industry is testing new potential drugs for their propensity to prolong human cardiac repolarization, and regards this as a sign of proarrhythmic risk. Many studies have dethroned the common perception that prolonged repolarization is a reliable surrogate marker for torsades de pointes (TdP) arrhyth...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1038/sj.bjp.0707299
更新日期:2007-08-01 00:00:00
abstract::1. This study was undertaken to investigate whether, after a brief exposure of guinea-pig isolated ileum and rabbit jejunum to bremazocine, a kappa-opioid agonist also possessing antagonist activity at mu-opioid receptors, the addition of opioid antagonists produced withdrawal contractures. Our aim was to verify in th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13334.x
更新日期:1995-03-01 00:00:00
abstract::1. The sinus node inhibitors UL FS 49 and DK-AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino-atrial (SA) node, which might originate from the use-dependent blockade of a hyperpolarization-activated current If. A hyperpolarization-activated current Ih, which is present in many types of neu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702153
更新日期:1998-10-01 00:00:00
abstract::1. Several amino-acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07056.x
更新日期:1968-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Red wine polyphenols (RWPs) inhibit the expression of vascular endothelial growth factor (VEGF), a major pro-angiogenic and pro-atherosclerotic factor, in vascular smooth muscle cells (VSMCs). The aim of this study was to identify which red wine polyphenols were inhibitory and to determine the me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706843
更新日期:2006-10-01 00:00:00
abstract::1. The present study characterized highly effective agonists from different classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of structure-activity relationships. 2. The high...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14927.x
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Adrenoceptors can associate with cardiac caveolae. To investigate the function of vascular caveolae, adrenoceptor-mediated effects were compared in the saphenous artery of caveolin-1 knockout (cav-1KO) and wild-type (WT) mice. EXPERIMENTAL APPROACH:Electronmicroscopy was used to detect caveolae....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706980
更新日期:2007-02-01 00:00:00
abstract::1. Calcium entry via neuronal calcium channels is essential for the process of neurotransmission. We investigated the calcium channel subtypes involved in the operation of cardiac autonomic neurotransmission by examining the effects of selective calcium channel blockers on the inotropic responses to electrical field s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702629
更新日期:1999-06-01 00:00:00
abstract::We studied the effects of the novel Na(+)/Ca(2+) exchange inhibitor KB-R7943, 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate, on the native nicotinic receptors present at the bovine adrenal chromaffin cells, as well as on rat brain alpha(3)beta(4) and alpha(7) nicotinic acetylcholine receptors (A...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703519
更新日期:2000-08-01 00:00:00
abstract::1. Voltage-operated calcium channel (VOCC) antagonists are effective antihypertensive and antianginal agents but they also depress myocardial contractility. 2. We compared four L-type calcium channel antagonists, felodipine, nifedipine, amlodipine and verapamil and a relatively T-type selective calcium channel antagon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702045
更新日期:1998-09-01 00:00:00
abstract::Botulinum toxin (Type A) depressed or abolished transmission from postganglionic nerves to smooth muscle of isolated preparations of guinea-pig and mouse vas deferens. The time course of blockade was 2 to 6 times slower than that observed with the same concentration of the same batch of toxin on the rat diaphragm. Spo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08343.x
更新日期:1973-02-01 00:00:00
abstract::1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of aut...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10507.x
更新日期:1983-05-01 00:00:00
abstract::1. The effects of cocaine, 6-hydroxydopamine (6-OHDA), reserpine and 17-beta-oestradiol on the sensitivity of the rat anococcygeus muscle to noradrenaline (NA), acetylcholine (ACh) and KCl were investigated.2. Cocaine (10(-5)M) increased the sensitivity of the anococcygeus to NA (100-fold) but not to ACh or KCl.3. 6-O...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb17261.x
更新日期:1973-11-01 00:00:00
abstract::1. Histamine release by compound 48/80 was substantially reduced in a time-dependent manner (maximum at 30 min) by pre-incubating mast cells in calcium-free medium at 37 degrees C but not at 2 degrees C. This effect was optimal at pH 7.0 to 7.5. 2. The re-introduction of calcium (0.1 to 3 mmol/l) restored histamine re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07871.x
更新日期:1979-04-01 00:00:00
abstract::It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702541
更新日期:1999-05-01 00:00:00
abstract::Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximatel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11116.x
更新日期:1986-09-01 00:00:00
abstract::1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706789
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13203
更新日期:2015-08-01 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
abstract::1 The possible involvement of N-methyl-D-aspartate (NMDA)-receptors in epileptiform synaptic activity in the kainic acid (KA) lesioned hippocampus was investigated. In this chronic model of epilepsy there is a loss of both the early and the late components of synaptic inhibition as well as changes in the membrane prop...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11280.x
更新日期:1987-08-01 00:00:00
abstract::Extensive in vitro and in vivo studies have shown that cannabinoid drugs have neuroprotective properties and suggested that the endocannabinoid system may be involved in endogenous neuroprotective mechanisms. On the other hand, neurotoxic effects of cannabinoids in vitro and in vivo were also described. Several possib...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01280.x
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Leucocyte infiltration is a rate-limiting step in the pathophysiology of acute pancreatitis (AP) although the adhesive mechanisms supporting leucocyte-endothelium interactions in the pancreas remain elusive. The aim of this study was to define the role of lymphocyte function antigen-1 (LFA-1) in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01225.x
更新日期:2011-05-01 00:00:00
abstract::1. The role of alpha- and beta-adrenoceptor subtypes in the regulation of plasma glucose and immunoreactive insulin (IRI) levels has been investigated in normal conscious fasted rats by employing selective agonists and antagonists. 2. Adrenaline (0.2 mg kg-1)-induced hyperglycaemia was abolished by the selective alpha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14078.x
更新日期:1990-08-01 00:00:00
abstract::The mechanism of action of prostacyclin (PGI2) on isolated segments of guinea-pig terminal ileum was studied by recording the changes in isometric tension. In these preparations PGI2 (1 nM-1 microM) caused a concentration-dependent increase in muscle tension. This effect was rapid and short-lasting. PGI2-induced contr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10031.x
更新日期:1983-10-01 00:00:00
abstract::1. The vasodilator responses of isolated intrapulmonary arteries (IPA) to P2-receptor agonists were investigated during adaptation to extrauterine life in the piglet. The effect of pulmonary hypertension on the normal response was determined after exposing newborn animals to chronic hypobaric hypoxia (51 kPa) for 3 da...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702815
更新日期:1999-10-01 00:00:00
abstract::1. We have investigated the effects of salmeterol (0.3-50 microM) on several pro-inflammatory activities of human neutrophils in vitro. 2. Oxidant production by FMLP- and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 microM) of salmeterol, while ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15297.x
更新日期:1996-04-01 00:00:00