Abstract:
:[3H]-guanfacine (N-amidino-2-(2,6-dichloro 3[3H] phenyl) acetamide hydrochloride; 24.2 Ci/mmol) has been used as a radioligand in homogenates of rat cerebral cortex. Specific binding of [3H]-guanfacine was linear with respect to tissue concentration (2.5-15 mg/ml), saturable and not markedly affected in the pH range 6.5-8.0. Analysis of the saturation of [3H]-guanfacine binding using an iterative least squares fitting procedure gave best fits to a single site model. [3H]-guanfacine binding was of high affinity (Kd 1.77 +/- 0.24 nM; n = 8) to a population of non interacting sites (nH 0.99 +/- 0.02; n = 8) with a density of 118.2 +/- 8.4 fmol/mg protein (n = 8). Highest levels of binding were achieved in cerebral cortex followed by thalamus greater than hypothalamus greater than medulla/pons greater than spinal cord greater than striatum greater than cerebellum. Binding was stereoselective with regard to the (-)-isomer of noradrenaline and the order of potency for displacement of [3H]-guanfacine by agonists was naphazoline greater than clonidine greater than (-)-adrenaline greater than (-)-alpha methylnoradrenaline greater than (-)-noradrenaline greater than (+/-)-alpha-methylnoradrenaline greater than (+)-noradrenaline greater than methoxamine greater than (+)-adrenaline greater than phenylephrine and by antagonists was phentolamine greater than dihydroergocryptine greater than piperoxane greater than yohimbine greater than prazosin greater than labetalol greater than indoramin suggested binding to alpha 2-adrenoceptors. The monovalent cations Na+ and K+ and also guanosine 5'-triphosphate (GTP) produced concentration-dependent inhibition whereas the divalent cations Ca2+, Mg2+, and Mn2+ first enhanced, then inhibited [3H]-guanfacine binding. Na+ (150 mM) or GTP (100 microM) produced marked reductions and Mn2+ (5 mM) marked increases in the number of receptor sites labelled by [3H]-guanfacine. 9 It is concluded that [3H]-guanfacine preferentially labels a high affinity state of the alpha 2- adrenoceptor in homogenates of rat cerebral cortex.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Jarrott B,Louis WJ,Summers RJdoi
10.1111/j.1476-5381.1982.tb08801.xsubject
Has Abstractpub_date
1982-02-01 00:00:00pages
401-8issue
2eissn
0007-1188issn
1476-5381journal_volume
75pub_type
杂志文章abstract::In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702025
更新日期:1998-08-01 00:00:00
abstract::1. Plasma exudation and blood flow changes induced by intradermal injection of prostaglandins E2 (PGE2), I2 (PG12), D2 (PGD2) and F2 alpha (PGF2 alpha) were measured in rabbit dorsal skin by the use of [131I]-albumin and 133Xe. 2. Little plasma exudation was produced by any of the prostaglandins when injected alone. 3...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07860.x
更新日期:1979-03-01 00:00:00
abstract::The effects of the alpha- and beta-isomers of flupenthixol on 5-hydroxytryptamine (5-HT)-induced platelet aggregation and on 5-HT and dopamine uptake were investigated. Alpha-Flupenthixol was 185 times more potent than the beta-isomer as an inhibitor of platelet aggregation. In contrast both isomers were equipotent a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07432.x
更新日期:1975-12-01 00:00:00
abstract::1. The GABA-B receptor agonists baclofen and 3-aminopropylphosphinic acid (3-APPi) have antitussive activity in the cat and guinea pig. The purpose of this study was to investigate the sites of action of these GABA-B receptor agonists to inhibit the cough reflex. 2. Single intracerebroventricular (i.c.v.) cannulas wer...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17145.x
更新日期:1994-12-01 00:00:00
abstract::1 A 3 min intracoronary infusion of adenosine (50 mug/min) produced a significant decrease in coronary artery perfusion pressure, left ventricular systolic pressure and myocardial O2 consumption in the isolated supported heart preparation of the dog perfused at a constant coronary blood flow. Heart rate was controlled...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07681.x
更新日期:1976-07-01 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:Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or an...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13121
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Exposure to an acute stress inhibits gastric emptying and stimulates colonic transit via central neuropeptide Y (NPY) pathways; however, peripheral involvement is uncertain. The anxiogenic phenotype of NPY(-/-) mice is gender-dependent, raising the possibility that stress-induced gastrointestinal...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.01939.x
更新日期:2012-08-01 00:00:00
abstract::1 In spontaneously active Purkinje fibres of young cows the dose-response curves of the action of isoprenaline upon different electrophysiological parameters were measured.2 The increase in slope of diastolic depolarization could roughly be described by a one-for-one binding curve with a half maximum effect near 10(-8...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07794.x
更新日期:1978-07-01 00:00:00
abstract::1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703425
更新日期:2000-07-01 00:00:00
abstract::1. We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in smooth mus...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704062
更新日期:2001-05-01 00:00:00
abstract::Cyclic adenosine monophosphate (cAMP) is one of the second messengers critically involved in the molecular mechanisms underlying memory formation. In the CNS, the availability of cAMP is tightly controlled by phosphodiesterase 4 (PDE4), a family of enzymes that degrades the cyclic nucleotide to inactive AMP. Among the...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13257
更新日期:2015-10-01 00:00:00
abstract::1. The blood pressure response to ranatensin, an undecapeptide from the skin of the frog, Rana pipiens, has been studied in various experimental animals.2. Ranatensin raised blood pressure in the dog and rabbit. The response was not altered by atropine, phentolamine, propranolol or hexamethonium, suggesting a direct p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10641.x
更新日期:1970-12-01 00:00:00
abstract::1. The effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on vasoconstrictor responses to transmural electrical nerve stimulation and noradrenaline were examined in the rabbit isolated renal artery with and without an intact endothelium. In addition, the effect of removing the end...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701141
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although botulinum toxin type A (BoNT/A) is approved for chronic migraine treatment, its mechanism of action is still unknown. Dural neurogenic inflammation (DNI) commonly used to investigate migraine pathophysiology can be evoked by trigeminal pain. Here, we investigated the reactivity of crania...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13366
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Melanin-concentrating hormone receptor 1 (MCH1 receptor) antagonists are being considered as anti-obesity agents. The present study reports a new class of MCH1 receptor antagonists with an 8-methylquinoline scaffold. The molecular mechanism of MCH1 receptor blockade by these antagonists was exami...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12529
更新日期:2014-03-01 00:00:00
abstract::1. Inhibition of nitric oxide generation with Nw-nitro-L-arginine (nitroarginine) reduced vasodilator responses to bradykinin and acetylcholine and enhanced those to nitroprusside in the rat isolated perfused kidney, preconstricted with phenylephrine. 2. Inhibition of cyclo-oxygenase with indomethacin, decreased the v...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14513.x
更新日期:1992-11-01 00:00:00
abstract::We investigated the action of the phenylalkylamines verapamil and N-methyl-verapamil on the Kv1.3 potassium channel using the whole-cell configuration of the patch-clamp technique. Our goal was to identify their binding as a prerequisite for using the phenylalkylamines as small, well-defined molecular probes, not only...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702599
更新日期:1999-07-01 00:00:00
abstract::1. The experiment investigated the effects of psychotropic drugs on enzymes in vitro.2. Chlorpromazine inhibits mitochondrial malate dehydrogenase in concentrations of 1.4x10(-4)M and above. No effect was observed below this concentration.3. A sharp inflection in the [unk]/drug plot was also seen with chlorpromazine (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb10582.x
更新日期:1969-10-01 00:00:00
abstract::1. Cannabinoids are potent inhibitors of endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations. We set out to study the mechanism underlying this effect and the possible role of cannabinoid-induced changes in intercellular gap junction communication. 2. In cultured endothelial cells, Delta(9)-tetrahyd...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704776
更新日期:2002-07-01 00:00:00
abstract::Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experimen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14598.x
更新日期:1989-11-01 00:00:00
abstract::1. A quantitative in vitro study has been made of the actions of glyceryl trinitrate and sodium nitrite on vascular smooth muscle (dog femoral artery and saphenous vein; rat portal vein); these have been compared with the actions of papaverine, isoprenaline, salbutamol, pentaerythritol tetranitrate and trimetazidine. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb16760.x
更新日期:1977-05-01 00:00:00
abstract::1. Pregnancy is characterized by a decrease in systemic vascular resistance and a blunting of the angiotensin II (AII) pressor response. We studied the role of nitric oxide (NO) and prostanoids in these vascular changes of pregnancy in anaesthesized, ganglion blocked non-pregnant and pregnant rats. 2. Inhibition of NO...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13297.x
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the rol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12584
更新日期:2014-05-01 00:00:00
abstract::1 Sera of rabbits immunized against a nocotinic receptor-rich fraction, obtained from the electric organ of Torpedo marmorata, were tested for their pharmacological activity on different in vitro preparations. 2 Sera containing antibodies against the nicotinic receptor blocked neuromuscular transmission in the phrenic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07651.x
更新日期:1976-05-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) is a relatively recently discovered molecule originating in the so-called L-cells of the intestine. The peptide has insulinotrophic properties and it is this characteristic that has predominantly been investigated. This has led to the use of the GLP-1-like peptide exendin-4 (EX-4), whic...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2009.00486.x
更新日期:2010-02-01 00:00:00
abstract::1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or nul...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701520
更新日期:1997-12-01 00:00:00
abstract::In anaesthetized dogs at room temperatures of 28-33 degrees C, the cerebral ventricles were perfused with artificial CSF from the left lateral ventricular to the aqueductal cannulae. The animals' temperatures were recorded from the rectum. Addition of Ca(++) in excess to the artificial CSF perfusing the ventricles pro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08547.x
更新日期:1973-12-01 00:00:00
abstract::1 The metabolism of extracellular nucleotides plays an important role in nucleotide signalling mediated by P2 receptors. The nucleotide sequence encoding a putative human ecto-ATPase named CD39L1 was reported recently. However, the biological activity of this protein has not been established. 2 Based on the sequence o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702805
更新日期:1999-09-01 00:00:00
abstract::1. The effectiveness of alpha 1- and alpha 2-adrenoceptor activation was compared at different levels of the saphenous and cephalic vein of the dog in vitro. 2. Helically cut strips were used to determine concentration-response curves to phenylephrine, noradrenaline, UK-14,304 (5-bromo-6-(imidazoline-2-ylamino)-quinox...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12719.x
更新日期:1990-10-01 00:00:00