Abstract:
:Binding of the 5-HT(7) receptor antagonist radioligand [(3)H]-SB-269970 to human 5-HT(7(a)) receptors expressed in HEK293 cell membranes (h5-HT(7(a))/293) and to guinea-pig cerebral cortex membranes, was characterized and compared with [(3)H]-5-CT binding. [(3)H]-SB-269970 (1 nM) showed full association with h5-HT(7(a))/293 membranes after 40 min. Specific binding at equilibrium represented >90% of total binding and was fully reversible by methiothepin (10 microM), full dissociation occurring by 100 min. The association (k(+1)) and dissociation (k(-1)) rate constants were 0.05 nM(-1)min(-1) and 0.05 min(-1) respectively, giving a K(D) (k(-1)/k(+1)) of 1.0 nM. [(3)H]-SB-269970 bound saturably and apparently monophasically to both h5-HT(7(a))/293 and guinea-pig cortex membranes, with K(D) values of 1.25+/-0.05 and 1.7+/-0.3 nM respectively. The B(max) for [(3)H]-SB-269970 to both h5-HT(7(a))/293 and guinea-pig cortex membranes (5780+/-380 and 125+/-8.2 fmoles mg protein(-1) respectively) was similar to that for [(3)H]-5-CT (6190+/-940 and 143+/-19 fmoles mg protein(-1) respectively). These data suggest that, in each tissue, both radioligands labelled the same population of receptors, which appear to be present in an agonist high affinity state. The profile of compound inhibition of [(3)H]-SB-269970 binding to h5-HT(7(a))/293 and guineapig cortex membranes correlated well (corr. coeff. 0.98) with those for [(3)H]-5-CT binding and were consistent with the profiles reported previously for the human 5-HT(7(a)) and guinea-pig cortex 5-HT(7) receptors using [(3)H]-5-CT. Hill slopes for inhibition of [(3)H]-SB-269970 and [(3)H]-5-CT binding were close to 1, consistent with binding to a single receptor population in both tissues. [(3)H]-SB-269970 represents the first selective 5-HT(7) antagonist radioligand, which should aid further characterization of 5-HT(7) receptors in recombinant and native tissues and help establish their role in brain function.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Thomas DR,Atkinson PJ,Ho M,Bromidge SM,Lovell PJ,Villani AJ,Hagan JJ,Middlemiss DN,Price GWdoi
10.1038/sj.bjp.0703318subject
Has Abstractpub_date
2000-05-01 00:00:00pages
409-17issue
2eissn
0007-1188issn
1476-5381journal_volume
130pub_type
杂志文章abstract::1. To investigate the role of nitric oxide in epilepsy we have studied the effects of agents which affect nitric oxide synthesis in sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is anticonvulsant in t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15690.x
更新日期:1996-09-01 00:00:00
abstract::The complement system plays a major role in threat recognition and in orchestrating responses to microbial intruders and accumulating debris. This immune surveillance is largely driven by lectins that sense carbohydrate signatures on foreign, diseased and healthy host cells and act as complement activators, regulators...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15307
更新日期:2020-11-03 00:00:00
abstract::1. We investigated the potent 5-hydroxytryptamine (5-HT)-mediated vasorelaxation of the sheep pulmonary vein. Here we present evidence that this response is due to activation of 5-HT4 receptors. 2. 5-HT (1-1000 nM) caused concentration-dependent, maintained relaxations (pEC50 = 8.4 +/- 0.1) of isolated rings of sheep ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12788.x
更新日期:1992-10-01 00:00:00
abstract::Ivabradine has proven therapeutic efficacy for cardiac ischaemia and, until proved otherwise, is a very specific inhibitor of the cardiac sinoatrial node I(f) current. In the current issue of the British Journal of Pharmacology, Drouin et al. demonstrated that chronic treatment of the human apoB-100 transgene dyslipid...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.168
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:JNJ-Q2, a novel broad-spectrum fluoroquinolone with anti-methicillin-resistant Staphylococcus aureus activity, was evaluated in a comprehensive set of non-clinical and clinical cardiovascular safety studies. The effect of JNJ-Q2 on different cardiovascular parameters was compared with that of mox...
journal_title:British journal of pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1476-5381.2012.01874.x
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Palmitoylethanolamide (PEA) is an endogenous congener of anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and at transient receptor potential vanilloid type-1 (TRPV1) channels. The other endocannabinoid, 2-arachidonoylglycerol (2-AG), was recently suggested to act as a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13084
更新日期:2016-04-01 00:00:00
abstract::The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the beta 1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb14582.x
更新日期:1986-04-01 00:00:00
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 con...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17168.x
更新日期:1994-12-01 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. Photoactivated mechanical responses that resulted from exposure to 3-NO2-1,4-dihydropyridines (3-NO2-DHP5) or NO-donors were examined in rat isolated oesophageal smooth muscle with a view to determining the role of calcium and cyclic GMP. 2. Isometric contractile force was recorded in preparations bathed in normal ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15138.x
更新日期:1995-12-01 00:00:00
abstract::1. The contribution of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) to non-adrenergic non-cholinergic (NANC) relaxations in the pig gastric fundus was investigated. 2. Circular and longitudinal muscle strips were mounted for isotonic registration in the presence of atropine and guanethidine; tone was ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16406.x
更新日期:1995-10-01 00:00:00
abstract::1. We aimed to determine whether there are any changes in responsiveness of the mesenteric arterial beds to phenylephrine (Phe) and KCl in exercise-trained rats, and whether vascular endothelium and/or vascular smooth muscle play a role in these changes. 2. Adult male rats were subjected to a swimming schedule every d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702697
更新日期:1999-08-01 00:00:00
abstract::1 Angiotensin I (AI) and AII elicited a dose-dependent potentiation of contractions by rat vas deferens produced by low frequency nerve stimulation without enhancing the contraction produced by exogenous noradrenaline. The AII-induced presynaptic potentiation was blocked by the specific antagonist cysteine(8)-AII.2 Th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09672.x
更新日期:1974-08-01 00:00:00
abstract::This article discusses the background to the need for change in the reporting of experiments involving animals, including a report of a consensus meeting organised by the Basel Declaration Society and Understanding Animal Research UK that sought to Internationalise guidelines for reporting experiments involving animal...
journal_title:British journal of pharmacology
pub_type: 社论
doi:10.1111/bph.12956
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:N-type voltage-gated calcium (Cav 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Cav 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13737
更新日期:2018-06-01 00:00:00
abstract::The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the seve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11195.x
更新日期:1987-03-01 00:00:00
abstract::The ability of chemically detoxified E. coli endotoxins and membrane-active agents to modify the toxicity of native E. coli endotoxin in vivo was examined. The time- and dose-dependent increase in plasma acid phosphatase activity following toxin administration to rats provided a convenient quantitative measure of in v...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb11015.x
更新日期:1983-06-01 00:00:00
abstract::1 The prostaglandin synthesizing enzymes were found to be present in fat cell ghosts isolated from rabbit adipose tissue. 2 Prostaglandin E2 (PGE2) and PGF2, were synthesized by ghosts after stimulation with adrenocorticotrophic hormone (ACTH). 3 Indomethacin was found to inhibit this synthesis but not the synthesis o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract::1. The present study was designed to test the hypothesis that beneficial effects of angiotensin converting enzyme (ACE)inhibitors are independent of a fall in blood pressure in rat experimental heart failure following coronary ligation. 2. The animals were assigned randomly to six groups; sham operation, controls subj...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13155.x
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Volume-regulated anion channels (VRACs) play an important role in cell-volume regulation. alpha(1)-Adrenoceptor stimulation by phenylephrine (PE) suppressed the hypotonic activation of VRAC current in mouse ventricular cells and regulatory volume decrease (RVD) was also absent in PE-treated cells...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00896.x
更新日期:2010-09-01 00:00:00
abstract::1. This study describes the effects of hypoxia on relaxing responses and cAMP production induced by the known vasodilator peptides: alphaCGRP, amylin (AMY) and adrenomedullin (AM) on isolated pig coronary arteries in vitro. 2. Hypoxic incubation increased the vasorelaxant effect of alphaCGRP (four-fold; P<0.05), AMY (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706232
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01453.x
更新日期:2012-02-01 00:00:00
abstract::1 Groups of mice were pretreated with the 5-hydroxytryptamine (5-HT) depletors, fenfluramine or p-chlorophenylalanine (PCPA), followed by pethidine or morphine. 2 Fenfluramine alone produced a short lasting analgesia but PCPA was without any effect. 3 Pethidine and morphine both increased hot plate reaction times meas...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09177.x
更新日期:1982-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with po...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01324.x
更新日期:2011-07-01 00:00:00
abstract::1. The class III antiarrhythmic azimilide has previously been shown to inhibit I(Ks) and I(Kr) in guinea-pig cardiac myocytes and I(Ks) (minK) channels expressed in Xenopus oocytes. Because HERG channels underly the conductance I(Kr), in human heart, the effects of azimilide on HERG channels expressed in Xenopus oocyt...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701575
更新日期:1998-01-01 00:00:00
abstract::1. Bepridil (BPD) is a pharmacological compound able to bind to the Ca2+ sensor protein troponin C (TnC), which triggers skeletal muscle contraction upon Ca2+-binding. BPD can thereby modulate the Ca2+-affinity of this protein. 2. The Ca2+-sensitizing action of bepridil was investigated on slow and fast isoforms of Tn...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702820
更新日期:1999-10-01 00:00:00
abstract::1 The effects of purported prostaglandin synthesis inhibitors on steroid and prostaglandin (E and F) release from trypsin-dispersed cat adrenocortical cells were investigated. 2 Low indomethacin concentrations potentiated adrenocorticotrophin (ACTH)-evoked prostaglandin and steroid release, whereas higher concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07477.x
更新日期:1976-06-01 00:00:00
abstract::1. Prostaglandin E2 (PGE2) is an autacoid that decreases proteoglycan synthesis, increases metalloprotease production by cultured chondrocytes, and can modulate some of the actions of interleukin-1 on cartilage. The objective of the present study was to characterize the subtype of prostaglandin E2 receptor present in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15580.x
更新日期:1996-08-01 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:BACKGROUND AND PURPOSE:Agonists of the M(2) muscarinic acetylcholine receptor (mAChR) increase mRNA for this receptor and mRNA for endothelial and neuronal isoforms of NO synthase (eNOS or nNOS). Here we examine the different signalling pathways involved in such events in rat cardiac atria. EXPERIMENTAL APPROACH:In is...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707180
更新日期:2007-05-01 00:00:00