Abstract：
:1. We investigated the mechanism of action of two novel nonsulphonylurea ATP-sensitive potassium channel (K(ATP)) inhibitors, PNU-99963 and PNU-37883A, on four types of cloned K(ATP) channels. 2. Whole-cell currents were recorded in a symmetrical potassium (140 mM) gradient in HEK-293 cells stably expressing Kir6.2/SUR1, Kir6.2/SUR2A, Kir6.2/SUR2B or Kir6.1/SUR2B. 3. PNU-99963 potently inhibited the four K(ATP) channel clones. The concentration at which half-maximum current was inhibited (IC(50)) was 66, 41, 43 and 11 nM for Kir6.2/SUR1, Kir6.2/SUR2A, Kir6.2/SUR2B and Kir6.1/SUR2B, respectively. In contrast, PNU-99963 up to a concentration of 3 microM had no significant effect on current generated in HEK-293 cells by transiently expressing Kir6.2Delta26, a C-terminal truncated pore-forming subunit of Kir6.2. 4. PNU-37883A inhibited four types of K(ATP) channels, but to different extents. Inhibition of the putative smooth muscle K(ATP) channel types, Kir6.2/SUR2B (IC(50); 15 microM) and Kir6.1/SUR2B (IC(50); 6 microM), was significantly greater than inhibition of either the pancreatic beta cell or cardiac K(ATP) channel clones. Moreover, PNU-37883A significantly inhibited currents generated by expressing Kir6.2Delta26 alone, with an IC(50) of 5 microM, which was significantly increased to 38 microM when Kir6.2Delta26 was expressed with SUR2B. 5. In conclusion, two structurally different nonsulphonylurea compounds, PNU-99963 and PNU-37883A, inhibit K(ATP) channels via different mechanisms, namely through the sulphonylurea receptor (SUR) and the pore-forming subunits, respectively, although SUR2B reduced the inhibitory effect of PNU-37883A. While PNU-99963 potently inhibits all the four cloned K(ATP) channels, PNU-37883A has a degree of selectivity towards both smooth muscle K(ATP) channels, but could not discriminate between them.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Cui Y,Tinker A,Clapp LHdoi
10.1038/sj.bjp.0705228subject
Has Abstractpub_date
2003-05-01 00:00:00pages
122-8issue
1eissn
0007-1188issn
1476-5381journal_volume
139pub_type
杂志文章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：:1. Muscarinic receptors on endothelial cells of bovine thoracic aorta were characterized by binding assays in which (-)-[3H]-N-methyl quinuclidinyl benzilate ([3H]-NMeQNB) was used as radioligand. 2. Binding of [3H]-NMeQNB to crude membranes of freshly isolated endothelial cells was atropine-displaceable and of high a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12181.x
更新日期：1991-02-01 00:00:00
abstract：:1. The effect of histamine H1-receptor stimulation on inositol phospholipid hydrolysis has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. Histamine (EC50 = 27 microM) stimulated the accumulation of [3H]-inositol phosphates in DDT1MF-2 cells prelabelled with [3H]-myo-inositol. 2-Thi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13462.x
更新日期：1993-01-01 00:00:00
abstract：:1. Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture. 2. Melatonin (10(-15) to 10(-13) M) induced pigment granule condensation; it was 10,000 times more effective than any ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07554.x
更新日期：1977-12-01 00:00:00
abstract：:5-Hydroxytryptamine (5-HT, 5-160 microgram kg-1) injected intravenously in pentobarbitone-anaesthetized, open-chest cats caused dose-dependent increases in pulmonary arterial and intratracheal pressures. There was also a marked systemic hypotension and bradycardia. The pulmonary effects were completely prevented by ke...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10033.x
更新日期：1983-10-01 00:00:00
abstract：:1. The oral sedative potencies of cannabis herb, crude ethanolic and petroleum-ether fractions, were assayed against delta'-trans-tetrahydrocannabinol (THC) administered orally to mice, by measuring spontaneous motor activity over 30 min periods, at selected times, up to 6 h. 2. The THC contents of the extracts were d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09145.x
更新日期：1981-04-01 00:00:00
abstract：:Resting blood flow, arterio-venous glucose and oxygen (A-V)O2 differences, glucose uptake and oxygen consumption by a segment of the upper jejunum were measured in anaesthetized dogs. Systemic arterial pressure was also measured. The effect of nicotine infusion (25 micrograms kg-1 i.v., over 10 min) on these measureme...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb11078.x
更新日期：1985-08-01 00:00:00
abstract：:1. 1-3(Chlorophenyl)piperazine (mCPP) (5 mg kg-1, i.p.) inhibited 2 h food intake in rats previously deprived of food for one day. Ten 5-hydroxytryptamine (5-HT) antagonists given s.c. opposed this hypophagic response. Calculated ID50 values correlated significantly with reported affinities (r = 0.81, n = 10, P less t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12369.x
更新日期：1991-08-01 00:00:00
abstract：:The chemical trimethylcyclohexanol (TMC) is closely related to menthol, the major component of a terpene preparation with known choleretic and cholelitholytic activity. Its effects on hepatic cholesterol synthesis and bile secretion were examined in the rat. In both acute and long-term dosing experiments TMC significa...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10759.x
更新日期：1984-01-01 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
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：:1. Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dys...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702856
更新日期：1999-10-01 00:00:00
abstract：:1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive compound tacrolimus (FK 506) and of two investigational drugs (KC11346 and KC12291). Using LC-MS (FK506) and HPLC-FL (K...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703062
更新日期：2000-01-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14146
更新日期：2018-04-01 00:00:00
abstract：:1. Contraction of the rabbit isolated saphenous vein is mediated by a heterogeneous endothelin (ET) receptor population. This study has characterized these receptor subtypes by use of several pharmacologically distinct ET receptor agonists and antagonists. 2. ET-1, ET-3, sarafotoxin S6c (STXc) and [Ala3,11]ET-1 produc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb14936.x
更新日期：1995-04-01 00:00:00
abstract：:1. Exogenous adenosine triphosphate (ATP) stimulated the short circuit current (SCC) in primary monolayer cultures of rat epididymal cells when added to the apical but not to the basolateral side of the monolayers. Half-maximal stimulation was achieved at 5 x 10(-8) M ATP. 2. The increase in SCC induced by ATP was dep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11770.x
更新日期：1988-12-01 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. The effects of some drugs known to inhibit transmission in the superior cervical ganglion and at the neuromuscular junction were investigated on the cholinergic nerve-smooth muscle junction, using the rat isolated innervated urinary bladder preparation.2. HC-3 and Win 4981 inhibited the indirectly evoked contractio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09900.x
更新日期：1970-08-01 00:00:00
abstract：:Drug induced long QT syndrome (LQTS) can lead to cardiac arrhythmias and sudden death, and has emerged as a worldwide problem. Most drugs that cause this are thought to directly block a specific cardiac ion channel (KCNH2 or hERG) that carries the rapidly activating delayed rectifier potassium current, I(Kr). In this ...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0706143
更新日期：2005-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14181
更新日期：2018-05-01 00:00:00
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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. The possibility that a purine nucleotide is involved in excitatory transmission to the urinary bladder has been tested. All the purine compounds tested which contained a pyrophosphate bond produced contraction, adenosine triphosphate (ATP) being the most potent. Adenosine and adenosine monophosphate caused relaxati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07283.x
更新日期：1972-03-01 00:00:00
abstract：:The ability of gamma-aminobutyric acid (GABA) to affect the release of [3H]-dopamine in rat brain synaptosomes prepared from corpus striatum, frontal cortex and hypothalamus and prelabelled with the radioactive catecholamine in the presence of desipramine was examined. GABA (10-300 microM) increased in a concentration...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb09004.x
更新日期：1987-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inflammasomes are multimeric complexes that facilitate caspase-1-mediated processing of the pro-inflammatory cytokines IL-1β and IL-18. Clinical hypertension is associated with renal inflammation and elevated circulating levels of IL-1β and IL-18. Therefore, we investigated whether hypertension i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13230
更新日期：2016-02-01 00:00:00
abstract：:Cannabinoid (CB1) receptor activation acts neuronally, reducing GI motility, diarrhoea, pain, transient lower oesophageal sphincter relaxations (TLESRs) and emesis, and promoting eating. CB2 receptor activation acts mostly via immune cells to reduce inflammation. What are the key questions which now need answering to ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707422
更新日期：2007-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Emesis is a multi-system reflex, which is usually investigated using in vivo models. The aim of the study is to compare the response induced by emetic compounds across species and investigate whether dogs, ferrets and rats are all similarly predictive of humans. EXPERIMENTAL APPROACH:A systemati...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01669.x
更新日期：2012-03-01 00:00:00
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：:A number of cholinoceptor antagonists used in the treatment of Parkinson's disease were examined for their ability to antagonize either the muscarinic receptor-mediated inhibition of dopamine D1 receptor-stimulated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [3H]-inositol phosphates ([3H]-IPs) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15474.x
更新日期：1996-06-01 00:00:00
abstract：:Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused o...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01711.x
更新日期：2012-04-01 00:00:00
abstract：:1. Rabbit left atrial preparations driven electrically at different rates were used for studies on inotropic effects of cations, drugs and coupled pacing. Sino-atrial node-atrial preparations were used for investigating the chronotropic effect of noradrenaline.2. The contractile tension-driving rate relationship was m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09510.x
更新日期：1969-06-01 00:00:00
