Abstract:
:1. A grease-gap technique has been used to measure d.c. potentials, in response to the application of excitatory amino acids and electrical stimulation of the Schaffer collateral-commissural pathway, in the CA1 region of rat hippocampal slices. The actions of L-glutamate (L-Glu) have been quantified and compared to those of structurally related compounds. 2. Perfusion of L-Glu (90s applications) depolarized the tissue with a threshold of approximately 50 microM and a maximum response in excess of 10 mM. L-Aspartate (L-Asp) produced a similar dose-response relationship. By comparison N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) were more potent excitants, producing dose-dependent depolarizations over the range 2-50 microM. 3. Application of the agonists depressed the amplitude of electrically-evoked synaptic responses; an effect that presumably reflects depolarization of neuronal tissue. However, for a given agonist-induced d.c. potential. L-Glu or L-Asp caused smaller depressions of synaptic responses than did either NMDA or AMPA. 4. The combined application of 50 microM D-2-amino-5-phosphonopentanoate (AP5) and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) substantially depressed synaptic responses and antagonized responses to NMDA and AMPA producing mean (+/- s.e.) dose-ratios of 12.2 +/- 1.2 and 7.0 +/- 0.8, respectively. However, these compounds produced minimal antagonism of responses to L-Glu and L-Asp (dose-ratios of 1.5 +/- 0.1 and 1.5 +/- 0.2, respectively). 5. Responses to the stereoisomers of homocysteate (HCA) were compared over the range 50 microM to 10 mM. D-HCA was approximately 3.6 times more potent than L-HCA and was antagonized to a greater extent by the combined application of 50 microM AP5 and 10 microM CNQX; the dose ratios were 8.7 + 0.8 and 5.1 + 0.9 for the D- and L- isomers, respectively. 6. The application of high doses of an excitant (e.g., 50mM L-Glu or 5mM D-HCA) caused an irreversible loss of sensitivity to NMDA and AMPA and abolished synaptic transmission. Responses to the other excitants were depressed by this excitotoxic lesion in the following order: D-HCA > L-HCA > L-Glu = LAsp. In slices treated in this manner, L-Glu, L-Asp and L-HCA produced very similar dose-response curves. 7. Some slices were unresponsive to NMDA, AMPA and electrical stimulation from the onset of the experiment but had sensitivity to L-Glu, L-Asp and L-HCA similar to that of slices that had received an excitotoxic lesion. 8. Slices that were experimentally lesioned, such that they became unresponsive to synaptic stimulation, AMPA and NMDA, were depolarized by a variety of compounds when tested at 5 mm. The D- and L- enantiomers of Asp and Glu produced similar responses and were slightly more active than quisqualate and threo-hydroxy-L-aspartate (THLA). Glycine, L-serine, D-serine, L-alanine and 4-aminobutanoate (GABA) elicited responses 15-30% of the size, while L-lysine, alpha-amino-isobutanoate and L-proline produced depolarizations of less than 10% of the size of those induced by 5mM L-Glu. NMDA and dihydrokainate were either inactive or induced small negative shifts in the d.c. potential. 9. We conclude that when hippocampal slices are perfused with L-Glu (or L-Asp) the main source of the depolarization is due to an interaction with an electrogenic carrier system.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Frenguelli BG,Blake JF,Brown MW,Collingridge GLdoi
10.1111/j.1476-5381.1991.tb12178.xsubject
Has Abstractpub_date
1991-02-01 00:00:00pages
355-62issue
2eissn
0007-1188issn
1476-5381journal_volume
102pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Increases in intracellular cyclic AMP (cAMP) augment the release/secretion of glucagon-like peptide-1 (GLP-1). As cAMP is hydrolysed by cAMP phosphodiesterases (PDEs), we determined the role of PDEs and particularly PDE4 in regulating GLP-1 release. EXPERIMENTAL APPROACH:GLP-1 release, PDE expre...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00194.x
更新日期:2009-06-01 00:00:00
abstract::1. We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702132
更新日期:1998-10-01 00:00:00
abstract::1. The inhibitory effect of caffeine on the calcium channel current was investigated in cultured myometrial cells isolated from pregnant rats. 2. Caffeine inhibited the calcium channel current elicited from a holding potential of -70 mV in a concentration-dependent manner. The IC50 was estimated to be 35 mM. 3. The ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12622.x
更新日期:1989-10-01 00:00:00
abstract::1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adreno...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08775.x
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13124
更新日期:2015-07-01 00:00:00
abstract::1. During the past few years it has been shown that the sympatholytic effect resulting from localized microinjection of clonidine and other imidazolines into the rostral ventrolateral medulla (RVL) results from activation of 'imidazoline' receptors (I1 receptors) rather than from an alpha 2-adrenoceptor-mediated effec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb14012.x
更新日期:1993-12-01 00:00:00
abstract::1. Despite the observation of pharmacological responses to neuropeptide Y (NPY) in mammalian kidneys, there are species differences in the ease with which specific NPY binding sites can be demonstrated; we have investigated whether this can be explained by differential metabolism of NPY by a membrane-bound peptidase. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12429.x
更新日期:1991-10-01 00:00:00
abstract::1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell recordings and monitoring the changes in intracellular free Ca2+ concentrati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16358.x
更新日期:1995-06-01 00:00:00
abstract::Ouabain was administered at a loading dose of 3 mug/kg followed by an infusion at a rate of 1 mug/kg-1 min-1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 mug/kg followed by an infusion at a rate of 3 mug kg-1 min-1 was administered to compare its effect ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06982.x
更新日期:1977-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1476-5381.2011.01620.x
更新日期:2012-03-01 00:00:00
abstract::1. TRPM8 (CMR1) is a Ca(2+)-permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin. It belongs to the transient receptor potential (TRP) family, and therefore is related to vanilloid receptor type-1 (VR1, TRPV1). We tested whether substances which are structurally related to ment...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705652
更新日期:2004-02-01 00:00:00
abstract::The protease inhibitor ritonavir is an integral part of current antiretroviral therapy targeting human immunodeficiency virus. Recent studies demonstrate that ritonavir induces apoptotic cell death with high efficiency in lymphoblastoid cell lines. Moreover, ritonavir can suppress activation of the transcription facto...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706023
更新日期:2004-12-01 00:00:00
abstract::1. The potassium current in embryo spinal neurones of Xenopus consists of at least two kinetically distinct components with overlapping voltage-dependencies of activation. We investigated whether capsaicin might specifically block these components in acutely dissociated neurones from stage 37/38 embryos by use of stan...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15680.x
更新日期:1996-09-01 00:00:00
abstract::1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an aff...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07372.x
更新日期:1975-03-01 00:00:00
abstract::1. We have evaluated the selectivity of ketoprofen and two novel nonsteroidal anti-inflammatory drugs, N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulphonamide (NS-398) and 5-methanesulphonamido-6-(2,4-difluorothiophenyl)-1-indano ne (L-745,337), in inhibiting the cyclo-oxygenase activity of prostaglandin endoperoxide s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15091.x
更新日期:1995-11-01 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
abstract:BACKGROUND AND PURPOSE:Dipyridamole enhances post-occlusive reactive hyperaemia (PORH) in the human forearm vascular bed. We hypothesize that this effect is completely mediated by increased adenosine receptor stimulation. To test this hypothesis, the effect of caffeine (an adenosine receptor antagonist) on dipyridamole...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.10
更新日期:2008-03-01 00:00:00
abstract::Almost all existing models for G-protein-coupled receptors (GPCRs) are based on the occurrence of monomers. Recent studies show that many GPCRs are dimers. Therefore for some receptors dimers and not monomers are the main species interacting with hormones/neurotransmitters/drugs. There are reasons for equivocal interp...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707571
更新日期:2008-03-01 00:00:00
abstract::The pharmacological properties of fatty acid amidohydrolase (FAAH) were investigated in brains of 35-day-old chickens, since nothing is known about the enzyme in avian species. FAAH activity towards both [(3)H]-palmitoylethanolamide (PEA) [K(M)=1.5 microM] and [(3)H]-anandamide (AEA) [K(M)=5.4 microM] was demonstrated...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703569
更新日期:2000-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-relat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01517.x
更新日期:2011-12-01 00:00:00
abstract::1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostanoid EP receptor ligands on vagally stimulated gastric acid secretion in rats anaesthetized with urethane. 2. Administration of misoprostol (EP3/EP2 receptor agonist) and sulprostone (EP3/EP1 receptor agonist) reduced vagally mediate...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15240.x
更新日期:1996-02-01 00:00:00
abstract::1. The pharmacology of the slow afterhyperpolarization (sAHP) was studied in cultured rat hippocampal pyramidal neurones. 2. Clotrimazole, its in vivo metabolite, 2-chlorophenyl-bisphenyl-methanol (CBM) and the novel analogues, UCL 1880 and UCL 2027, inhibited the sI(AHP) with similar IC50s (1-2 microM). 3. Clotrimazo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703895
更新日期:2001-02-01 00:00:00
abstract::This work investigates the receptor acted upon by imidazoline compounds in the modulation of morphine analgesia. The effects of highly selective imidazoline ligands on the supraspinal antinociception induced by morphine in mice were determined. 2. Intracerebroventricular (i.c.v.) or subcutaneous (s.c.) administration ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703294
更新日期:2000-05-01 00:00:00
abstract::1. The effects of intravenous administration of two alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of single neurones to iontophoretically applied excitatory amino acids. The tests were performed on spinal neurones in alpha-chloralose anaesthetized, spinalized rat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13156.x
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Positive modulators of small conductance Ca(2+)-activated K(+) channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non-excitable cells. The prototype compound 1-EBIO or the more potent compound NS309, do not distinguish between the SK subtypes a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707281
更新日期:2007-07-01 00:00:00
abstract::1. Recent studies have shown antagonists at the NK1 subtype of receptor for tachykinins are antiemetics and suggested that this may result from blockade of tachykinin-mediated synaptic transmission at a central site in the emetic reflex. 2. We have used intracellular recording in vitro to study the pharmacology of tac...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701482
更新日期:1997-11-01 00:00:00
abstract::1. Superoxide dismutase (SOD, 60 u ml-1) or ferricytochrome c (70 microM) significantly inhibited thrombin-stimulated platelet adhesion to gelatin-coated plastic, whereas catalase (1000 u ml-1) or mannitol (1 mM) had no effect. 2. The platelet aggregation induced by low concentrations of thrombin (causing less than 45...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12572.x
更新日期:1989-08-01 00:00:00
abstract::In this issue MacMillan and McCarron in 2010 demonstrated that the phospholipase C (PLC) inhibitor U-73122 can potently inhibit Ca(2+) release from isolated smooth muscle cells independent of its effect on PLC. Their data suggest that the PLC inhibitor can block the sarcoplasmic/endoplasmic reticulum calcium ATPase pu...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2010.00795.x
更新日期:2010-07-01 00:00:00
abstract::1. The specificity of several ganglion stimulants has been tested on the isolated guinea-pig ileum by measuring the dose ratios produced by concentrations of hexamethonium.2. Most ganglion stimulants are also active at postganglionic receptors, some as blocking agents (for example, lobeline and dimethylphenylpiperazin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07093.x
更新日期:1971-05-01 00:00:00
abstract::Little is known about the intracellular actions of imipramine (IMI) in the regulation of ion channels. We tested the action of IMI on the intracellular cascade that regulates M current (I(M)) in superior cervical ganglion neurones (SCGs). Dialysis of the cells with GDPbetaS, a G protein signaling blocker, did not disr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706239
更新日期:2005-07-01 00:00:00