Abstract:
:1. The tachykinin receptor mediating contraction of the guinea-pig isolated proximal urethra has been characterized by use of receptor selective agonists and antagonists. All experiments were performed in the presence of peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each) in order to reduce peptide degradation. 2. The natural tachykinins, substance P and neurokinin A produced a concentration-dependent contraction of rings of the proximal urethra which approached the same maximum (about 50% of the response to 80 mM KCl). Substance P (EC50 155 nM) was slightly (3.6 times) more potent than neurokinin A (EC50 560 nM). 3. The tachykinin NK1 receptor selective agonist, [Sar9]substance P sulphone (EC50 62 nM), was slightly more potent than substance P and produced the same maximal response of natural tachykinins. The NK2 receptor selective agonist, [beta Ala8] neurokinin A(4-10), was active only at microM concentrations and its maximal effect did not exceed 20% of that to substance P or neurokinin A. The NK3 receptor selective agonist, senktide, was ineffective up to 30 microM. 4. The response to [Sar9]substance P sulphone was antagonized in a competitive manner by either (+/-)-CP 96,345 (pA2 7.75, slope - 1.10) or GR 82,334 (pA2 7.31, slope - 1.26), which are selective NK1 receptor antagonists, while it was unaffected (up to 10 microM) by MEN 10,376, a selective NK2 receptor antagonist. 5. The response to 10 microM [beta Ala8]neurokinin A (4-10) was abolished by either 0.2 microM (+/-)-CP 96,345 or 1 microM GR 82,334, suggesting the involvement of NK1 receptors.6. Electrical field stimulation (5 and 10 Hz, 0.25 ms, 100 V, trains of 5 s duration) produced tetrodotoxin-sensitive phasic contractions of the urethra which were abolished by atropine plus phentolamine (3 microM each). Capsaicin (1 microM) produced a small transient contraction of the urethra which was abolished by ( )-CP 96,345 (0.1 microM). ( )-CP 96,345 did not modify the response to electrical field stimulation.7. We conclude that tachykinin NK, receptors are the main if not the only mediators of the contractile response of guinea-pig proximal urethra to peptides of this family and that this preparation is useful for assessing the affinities of various ligands for the NK, receptor. Endogenous tachykinins released from peripheral endings of capsaicin-sensitive primary afferents produce urethral contraction by activating NK, receptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Maggi CA,Patacchini Rdoi
10.1111/j.1476-5381.1992.tb14430.xsubject
Has Abstractpub_date
1992-08-01 00:00:00pages
888-92issue
4eissn
0007-1188issn
1476-5381journal_volume
106pub_type
杂志文章abstract::Zanapezil (TAK-147 (3-[1benzylpiperdin-4-yl]-1-(2,3,4,5-tetrahydro-1 H-1-benzazepin-8-yl) propan-1-one fumarate)) is a selective acetylcholine (ACh) esterase inhibitor under investigation as a drug for Alzheimer's disease (AD) treatment. In this study, the effects of TAK-147 at 2 mg kg(-1) p.o. for 21 days, compared t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706288
更新日期:2005-08-01 00:00:00
abstract::1. The present study was undertaken to investigate the effects of the novel nociceptin receptor antagonist, [Nphe(1)]-Nociceptin (1-13)-NH(2) (bilateral intrahippocampal injection, 50 nmole rat(-1)) on purported nociceptin-induced (bilateral intrahippocampal injection, 5 nmole rat(-1)) deficits in spatial learning in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703724
更新日期:2000-12-01 00:00:00
abstract::1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0700885
更新日期:1997-01-01 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::Airway hyper-reactivity to inhaled adenosine, mediated via mast cell activation, is a cardinal feature of asthma. Animal models have been developed in several species to mimic this phenomenon, but only in the rat has a mast cell involvement been clearly defined. In this study, a model of ovalbumin-induced adenosine hy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706271
更新日期:2005-08-01 00:00:00
abstract::The effects of N-(cyclopropylmethyl)-19-isopentylnororvinol hydrochloride (M320) on urine excretion by rats were investigated. Further studies, using rabbit isolated vas deferens, investigated its interactions with kappa-opiate receptors. The output of urine for a 2 h period after M320, administered subcutaneously to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11180.x
更新日期:1986-12-01 00:00:00
abstract::Cholesterol and oxysterol sulfates are important regulators of lipid metabolism, inflammation, cell apoptosis, and cell survival. Among the sulfate-based lipids, cholesterol sulfate (CS) is the most studied lipid both quantitatively and functionally. Despite the importance, very few studies have analysed and linked th...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15227
更新日期:2020-08-06 00:00:00
abstract:BACKGROUND AND PURPOSE:Due to their potent bronchodilator properties, beta(2)-adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of beta(2)-adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of beta(2)-adrenoceptor agonists on inflammatory me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00708.x
更新日期:2010-05-01 00:00:00
abstract::In moderate-to-severe asthma, adding an inhaled long-acting β2 -adenoceptor agonist (LABA) to an inhaled corticosteroid (ICS) provides better disease control than simply increasing the dose of ICS. Acting on the glucocorticoid receptor (GR, gene NR3C1), ICSs promote anti-inflammatory/anti-asthma gene expression. In vi...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13628
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:To determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac(1) and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs). EXPERIMENTAL APPROACH:hVSMCs were incubated with xanthine-xanthine oxidase (X-XO; a superoxide generating sy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.300
更新日期:2008-11-01 00:00:00
abstract::The effect of acute, streptozotocin-induced diabetes on the affinity (KD), density (Bmax) and selectivity of specific, high affinity binding sites for [125I]-endothelin [( 125I]-ET) in rat cardiac membrane fragments was determined. Three days after a single i.v. bolus dose of streptozotocin (60 mg kg-1), the density o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12552.x
更新日期:1989-08-01 00:00:00
abstract::1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17004.x
更新日期:1994-10-01 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. The effects of melanotrophin release inhibiting factor (MIF) and its cyclic analogue cyclo (Leu-Gly) on tolerance to the analgesic effect of morphine were studied in male Sprague-Dawley rats. 2. Tolerance to morphine was induced by implantation of four morphine pellets (each containing 75 mg of morphine free base) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09152.x
更新日期:1981-04-01 00:00:00
abstract::Cartilage destruction is a key characteristic of arthritic disease, a process now widely established to be mediated by metzincins such as MMPs. Despite showing promise in preclinical trials during the 1990s, MMP inhibitors for the blockade of extracellular matrix turnover in the treatment of cancer and arthritis faile...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14173
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pharmacokinetic/pharmacodynamic (PK/PD) models are necessary to relate the degree of drug exposure in vivo to target blockade and pharmacological efficacy. This manuscript describes a murine agonist-induced CXCR3 receptor internalization assay and demonstrates its utility for PK/PD analyses. EXP...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707519
更新日期:2007-12-01 00:00:00
abstract::1. The effects of 3 competitive N-methyl-D-aspartate (NMDA) receptor antagonists, LY274614, LY233536 and LY235723, on the micturition reflex and external urethral sphincter EMG activity, were examined either under isovolumetric conditions or during continuous filling cystometry in urethane-anaesthetized (1.2 g kg-1, s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13774.x
更新日期:1993-09-01 00:00:00
abstract::1 alpha-Flupenthixol (alpha-FPT; 0.2 mg/kg i.p.) when administered to rats produced catalepsy. 2 Baclofen (10 mg/kg i.p.) given 30 min after alpha-FPT had a biphasic effect on the catalepsy. Initially there was a potentiation of the effect, followed by a significant attenuation of the degree of catalepsy. 3 Possible m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08460.x
更新日期:1978-02-01 00:00:00
abstract::The consumption of green tea (Camellia sinensis) has been shown to have many physiological and pharmacological health benefits. In the past two decades several studies have reported that epigallocatechin-3-gallate (EGCG), the main constituent of green tea, has anti-infective properties. Antiviral activities of EGCG wi...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12009
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In endothelial dysfunction, signalling by nitric oxide (NO) is impaired because of the oxidation and subsequent loss of the soluble guanylyl cyclase (sGC) haem. The sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino)methyl[benzoic]acid (BAY 58-2667) is a haem-mimetic abl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00263.x
更新日期:2009-07-01 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:BACKGROUND AND PURPOSE:Certain 5-lipoxygenase (5-LO) inhibitors exhibit anti-carcinogenic activities against 5-LO overexpressing tumour types and cultured tumour cells. It has been proposed therefore that 5-LO products significantly contribute to tumour cell proliferation. To date, the relationship between the inhibito...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00915.x
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Orally administered withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of withanoside IV, was identified as an active metabolite after ora...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00313.x
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Heat-sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is well established in the distal nephron; however, we have no data about their presence in podocytes. As podocytes are ind...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14052
更新日期:2017-12-01 00:00:00
abstract::Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and inhibits stimulated adenylate cyclase. Adenosine 5'-O-(1-thiodiphosphate) (ADP-alpha-S) and adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) act at the ADP receptor and achieve the same maximal rate of human platelet aggregation as each other. Adenos...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08781.x
更新日期:1982-02-01 00:00:00
abstract::1. Two quinozalinediones, FG9041 and FG9065, which had previously been shown to displace binding to the quisqualate receptor, were tested on rat neocortex and frog spinal cord in vitro against depolarizations induced by quisqualate, kainate and N-methyl-D-aspartate (NMDA). In both preparations effects of quisqualate w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11680.x
更新日期:1988-10-01 00:00:00
abstract::1 We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n-butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into eosinophils. 2 Viability of the cells incubated with apicidin (100 nm), TSA (30 nm) or n-butyrate...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705869
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffnes...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13223
更新日期:2015-09-01 00:00:00
abstract::1 Contractile responses produced by the alpha 1-adrenoceptor selective agonist, phenylephrine, and the alpha 2-adrenoceptor selective agonists, oxymetazoline and clonidine, have been compared to those produced by noradrenaline (non selective) in the rat aorta. 2 The relative order of potency of the agonists was noradr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09337.x
更新日期:1982-12-01 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