Abstract:
:1. Cumulative concentration-response curves (CRC) to prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2alpha (0.01-30 microM) and to the thromboxane A2 (TXA2) receptor agonist U-46619 (0.01-30 microM) were constructed in human isolated detrusor muscle strips both in basal conditions and during electrical field stimulation. 2. All the agonists tested contracted the detrusor muscle. The rank order of agonist potency was: PGF2alpha > U-46619 > PGE2 whereas weak contractile responses were obtained with PGD2 and PGE1. Any of the agonists tested was able to induce a clear plateau of response even at 30 microM. 3. The selective TXA2 antagonist, GR 32191B (vapiprost), antagonized U-46619-induced contractions with an apparent pK(B) value of 8.27+/-0.12 (n = 4 for each antagonist concentration). GR 32191B (0.3 microM) did not antagonize the contractile responses to PGF2alpha and it was a non-surmountable antagonist of PGE2 (apparent pK(B) of 7.09+/-0.04; n = 5). The EP receptor antagonist AH 6809 at 10 microM shifted to the right the CRC to U-46619 (apparent pK(B) value of 5.88+/-0.04; n = 4). 4. Electrical field stimulation (20 Hz, 70 V, pulse width 0.1 ms, trains of 5 s every 60 s) elicited contractions fully sensitive to TTX (0.3 microM) and atropine (1 microM). U-46619 (0.01-3 microM) potentiated the twitch contraction in a dose-dependent manner and this effect was competitively antagonized by GR 32191B with an estimated pK(B) of 8.54+/-0.14 (n = 4 for each antagonist concentration). PGF2alpha in the range 0.01-10 microM (n = 7), but not PGE2 and PGE1 (n = 3 for each), also potentiated the twitch contraction of detrusor muscle strips (23.5+/-0.3% of KCl 100 mM-induced contraction) but this potentiation was unaffected by 0.3 microM GR 32191B (n = 5). 5. Cumulative additions of U-46619 (0.01-30 microM) were without effect on contractions induced by direct smooth muscle excitation (20 Hz, 40 V, 6 ms pulse width, trains of 2 s every 60 s, in the presence of TTX 1 microM; n = 3). Moreover, pretreatment of the tissue with 0.3 microM U-46619 did not potentiate the smooth muscle response to 7 microM bethanecol (n = 2). 6. We concluded that TXA2 can induce direct contraction of human isolated urinary bladder through the classical TXA2 receptor. Prostanoid receptors, fully activated by PGE2 and PGF2alpha are also present. All these receptors are probably located post-junctionally. The rank order of agonist potency and the fact that GR 32191B, but not AH6809, antagonized responses to PGE2 seem to indicate the presence of a new EP receptor subtype. Moreover, we suggest the presence of prejunctional TXA2 and FP receptors, potentiating acetylcholine release from cholinergic nerve terminals.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Palea S,Toson G,Pietra C,Trist DG,Artibani W,Romano O,Corsi Mdoi
10.1038/sj.bjp.0701903subject
Has Abstractpub_date
1998-07-01 00:00:00pages
865-72issue
5eissn
0007-1188issn
1476-5381journal_volume
124pub_type
杂志文章abstract::We have investigated the effects of methylenedioxymethamphetamine (MDMA, 'ecstasy'), i.v., on diastolic blood pressure (DBP) in pithed and pentobarbitone anaesthetized rats. In pithed rats, the non-selective 5-HT receptor antagonist methiothepin (0.1 mg kg(-1)) and the alpha2-adrenoceptor antagonists methoxyidazoxan a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704094
更新日期:2001-06-01 00:00:00
abstract::1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM) produ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12754.x
更新日期:1992-10-01 00:00:00
abstract::1. The degree to which the RhoA kinase (ROK) blockers, Y-27632 (1 micro M) and HA-1077 (10 micro M), and the PKC blocker, GF-109203X (1 micro M), reduced force produced by carbachol, a muscarinic receptor agonist, and phenylephrine, an alpha-adrenoceptor agonist, was examined in rabbit stomach fundus smooth muscle. 2....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704952
更新日期:2002-12-01 00:00:00
abstract::1 Urocortin is a vasodilator peptide related to corticotrophin-releasing factor, which may protect endothelial function during coronary ischemia-reperfusion (I-R). The aim of this study was to study the mechanisms of this protective effect. 2 Hearts from Sprague-Dawley rats were isolated and perfused at constant flow ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706208
更新日期:2005-06-01 00:00:00
abstract::N-methyl-d-aspartate (NMDA) receptors have been demonstrated to be a pivotal target for ethanol action. The present study examined the actions of acute ethanol exposure on NMDA-induced responses and the acute tolerance to ethanol actions in rat sympathetic preganglionic neurons (SPNs) in vitro and in vivo. NMDA (50 mi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705512
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASS...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12193
更新日期:2013-07-01 00:00:00
abstract::1 We have investigated the effects of loperamide on intracellular Ca(2+) stores and membrane K(+) channels in insulin-secreting hamster insulinoma (HIT-T15) cells. 2 In cell-attached patch-clamp mode, loperamide (3-250 micro M) activated large single-channel currents. The loperamide-activated currents were tentatively...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705263
更新日期:2003-05-01 00:00:00
abstract::1 4-Aminopyridine methiodide (4-APMI), a quaternary analogue of aminopyridine (4-AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve-muscle preparations. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) augmented indirectly elicited twitches and reversed tubocurari...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb17333.x
更新日期:1979-01-01 00:00:00
abstract::Topical ophthalmic formulations of analogues of the endogenous arachidonic acid cyclooxygenase metabolite, PGF2α , are the standard of care treatment for the blinding disease glaucoma. These are the most potent and efficacious medical therapies for lowering intraocular pressure (IOP), the most important risk factor id...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14327
更新日期:2019-04-01 00:00:00
abstract::1. Modulation by nitric oxide (NO) of the ATP-sensitive K+ channel (KATP) current (IK(ATP)) was investigated in single ventricular cells dissociated from guinea-pig hearts. IK(ATP) was induced by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine+ ++ (KRN4884) and cromakalim. 2. In the whole-cell pat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701069
更新日期:1997-04-01 00:00:00
abstract::1 A series of cationic, lipophilic histamine H1-receptor antagonists, neuroleptics, antidepressants and monoamine oxidase inhibitors were tested for their effects on anti-IgE-induced histamine release from human lung fragments in vitro. 2 They had a biphasic effect: at low concentrations a dose-related inhibition of h...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb07919.x
更新日期:1980-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Iridoid glycosides containing the double bond scaffold of cyclopentapyran are reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and exert anti-nociceptive and neuroprotective actions. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical se...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13720
更新日期:2017-04-01 00:00:00
abstract::NO is a neurotransmitter released from enteric inhibitory neurons and responsible for modulating gastrointestinal (GI) motor behaviour. Enteric neurons express nNOS (NOS1) that associates with membranes of nerve varicosities. NO released from neurons binds to soluble guanylate cyclase in post-junctional cells to gener...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14459
更新日期:2019-01-01 00:00:00
abstract::1. The effects of dopamine on the L-type Ca2+ current (ICa,L) of both atrial and ventricular single myocytes and on the force of contraction of atrial trabeculae in rat heart were investigated. 2. Dopamine increased atrial ICa,L at concentrations higher than 1 microM, but had little or no effect on ICa,L at lower conc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701250
更新日期:1997-08-01 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::It was confirmed that morphine administration in vivo produced a selective decrease in the calcium content of synaptosomal fractions prepared from rat cerebral cortices. This effect was prevented by naloxone. 2 After morphine or naloxone, there were no changes in the sodium, potassium and magnesium contents of any of ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb10379.x
更新日期:1976-08-01 00:00:00
abstract::1. Prostanoids induce a wide range of biological actions which are mediated by specific membrane-bound receptors. We have recently shown that the E-type prostaglandins, PGE1 and PGE2, effectively inhibit eosinophil aggregation induced by platelet-activating factor (PAF). In an attempt to determine which prostanoid rec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701107
更新日期:1997-05-01 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::1. Column chromatography with Agarose A50m followed by Sephadex G100 was used to separate a fraction (extract II) in the molecular weight range 12,000 to 14,000 daltons from saline extracts of the sea anemone, Tealia felina. 2. Extract II inhibited histamine-induced contractions of the guinea-pig ileum and produced ha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09115.x
更新日期:1981-02-01 00:00:00
abstract::1 We investigated the neuritogenic action of nitric oxide (NO)-generating agents and their mechanisms of action in a subclone of rat pheochromocytoma, PC12h cells. 2 NO donors such as sodium nitroprusside (SNP, 0.05-1 microM), NOR1 (5-100 microM), NOR2 (5-20 microM), NOR3 (5-20 microM), NOR4 (5-100 microM), or S-nitro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706370
更新日期:2005-11-01 00:00:00
abstract::1. Pithed rats were respired at a fixed rate of 54 cycles min-1 and with a ventilation volume of either 20 (control) or 10 ml kg-1. In these two preparations, the dose-response relationships for the systemic blood pressure responses to endothelin-1, administered i.v., were examined. Also, cardiac output, its distribut...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14638.x
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01391.x
更新日期:2011-09-01 00:00:00
abstract::1. Opioid agonists inhibit neurogenic mucus secretion in the airways. The mechanism of the inhibition is unknown but may be via opening of potassium (K+) channels. We studied the effect on neurogenic secretion in ferret trachea in vitro of the OP1 receptor (formerly known as delta opioid receptor) agonist [D-Pen2,5]en...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701786
更新日期:1998-04-01 00:00:00
abstract::1 Uniaxial cyclic stretch leads to an upregulation of cyclooxygenase (COX)-2 through increases in the intracellular Ca(2+) concentration via the stretch-activated (SA) channel and following nuclear factor kappa B (NF-kappaB) activation in human fibroblasts. However, the signaling mechanism as to how the elevated Ca(2+...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706182
更新日期:2005-06-01 00:00:00
abstract::1. The mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701932
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12690
更新日期:2014-07-01 00:00:00
abstract::We studied the effects of endothelium-derived relaxing factor (EDRF), bovine retractor penis muscle inhibitory factor and sodium nitroprusside, three stimulants of guanylate cyclase, on the in vitro aggregation of washed human platelets. Platelet aggregation induced either by collagen or by the thromboxane A2 analogue...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11221.x
更新日期:1987-04-01 00:00:00
abstract::ST-segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open-chest anaesthetized dogs. This was greatly reduced by the prior administration of the anti-dysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the exte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08421.x
更新日期:1977-10-01 00:00:00
abstract::1. Sympathetic neurotransmission and noradrenaline content of the tail artery of Wistar rats treated for 7 days with the adenosine antagonist, 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), were examined. 2. Systolic blood pressure of the DPSPX-treated rats (164.0 +/- 2.9 mmHg; n = 6) was significantly greater than sali...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16683.x
更新日期:1995-09-01 00:00:00
abstract::At nanomolar concentrations, SR141716 and AM251 act as specific and selective antagonists of the cannabinoid CB1 receptor. In the micromolar range, these compounds were shown to inhibit basal G-protein activity, and this is often interpreted to implicate constitutive activity of the CB1 receptors in native tissue. We ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705577
更新日期:2003-12-01 00:00:00