Abstract：
:(1) Rapid desensitization of ligand-gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast-channel activation difficult. Investigation of the antagonist pharmacology of ATP-sensitive homomeric P2X3 receptors is limited by agonist-evoked fast-desensitization kinetics. (2) In the present studies, chimeric receptors were created using the coding sequence for the N-terminus and the first transmembrane domain of either the nondesensitizing human P2X2a or fast-desensitizing P2X3 receptor joined to the sequence encoding the extracellular loop, second transmembrane domain, and C-terminus of the other receptor (designated P2X2-3 and P2X3-2, respectively). These clones were stably transfected into 1321N1 astrocytoma cells for biophysical and pharmacological experiments using both electrophysiological and calcium-imaging methods. (3) Chimeric P2X2-3 and P2X3-2 receptors were inwardly rectifying and agonist responses showed desensitization properties similar to the wild-type human P2X2a and P2X3 receptors, respectively. (4) The P2X2-3 chimera displayed an agonist pharmacological profile similar to the P2X3 wild-type receptor being activated by low concentrations of both ATP and alpha,beta-meATP. In contrast, the P2X3-2 chimera had markedly reduced sensitivity to both agonists. (5) The P2X3 receptor antagonists TNP-ATP and A-317491 were shown to be potent, competitive antagonists of the P2X2-3 chimera (Ki=2.2 and 52.1 nm, respectively), supporting the hypothesis that rapid receptor desensitization can mask the competitive antagonism of wild-type homomeric P2X3 receptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Neelands TR,Burgard EC,Uchic ME,McDonald HA,Niforatos W,Faltynek CR,Lynch KJ,Jarvis MFdoi
10.1038/sj.bjp.0705411subject
Has Abstractpub_date
2003-09-01 00:00:00pages
202-10issue
1eissn
0007-1188issn
1476-5381pii
sj.bjp.0705411journal_volume
140pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Histamine modulates several behaviours and physiological functions, and its deficiency is associated with neuropsychiatric disorders. Gestational intake of valproic acid (VPA) is linked to autism spectrum disorder (ASD), characterized by impaired sociability and stereotypies. VPA effects on the n...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14124
更新日期：2018-03-01 00:00:00
abstract：:1. This study investigated whether (a) cannabinoid CB(1) receptor knockout (CB(1)(-/-)) mice displayed altered gastrointestinal transit and (b) cannabinoid CB(1) and opioid receptors functionally interact in the regulation of gastrointestinal transit. 2. Gastrointestinal transit was assessed by the Whole Gastrointesti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706824
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abstract：:1 Noradrenaline and 28 imidazolidine (clonidine-like) and imidazoline (oxymetazoline-like) compounds with various phenyl ring substituents have been examined for their ability to inhibit responses to transmural stimulation and exogenous acetylcholine in ileal preparations from reserpine-treated guinea-pigs.2 The bathi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb10429.x
更新日期：1981-06-01 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
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abstract：:1. Muscarinic receptors present in the human astrocytoma cell line 1321 N1 were characterized in radioligand binding studies and in functional studies of carbachol-stimulated phosphatidylinositol (PI) turnover. 2. In radioligand binding studies the muscarinic receptor in intact cells could be labelled using [3H]-N-met...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1989.tb11813.x
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abstract：:1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701767
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abstract：:The effect of the imidazolidine Sgd 101/75 (2-[2-methylindazol-4-imino]-imidazolidine HCl) on blood pressure, as well as its alpha-adrenoceptor agonist activity and affinity for these receptors, were examined in various animal preparations. After both intravenous administration to conscious spontaneously hypertensive ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10072.x
更新日期：1984-02-01 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
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doi：10.1038/sj.bjp.0707180
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701710
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15412.x
更新日期：1996-05-01 00:00:00
abstract：:1. The calcium sensitivity of force production of cardiac muscle fibres is altered by certain drugs. The sites of action of three such compounds (pimobendan, sulmazole, isomazole) within the myofibril have been investigated. Calmodulin antagonists, perhexilene and bepridil, which have been shown to alter the calcium d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14092.x
更新日期：1990-08-01 00:00:00
abstract：:1. SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2 ,3-f]indole) displays a high affinity (pK1 7.9) for the cloned human 5-HT2C receptor expressed in HEK 293 cells and the 5-HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation. SB 206553 has low affinity for cloned human 5-HT...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1996.tb15208.x
更新日期：1996-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. EXPERIMENTAL APPROACH:Concentrations of reactive...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00704.x
更新日期：2010-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704768
更新日期：2002-06-01 00:00:00
abstract：:The cardiovascular effects of doxazosin, a quinazoline derivative related to prasozin were investigated and compared to prazosin in the rabbit. Radioligand binding studies using rabbit cerebral membranes showed that both doxazosin and prazosin were roughly equipotent at displacing [3H]-prazosin from specific binding s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb09437.x
更新日期：1985-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09610.x
更新日期：1974-03-01 00:00:00
abstract：:1. The effect of in vivo desensitization to leukotriene B4 (LTB4) on eosinophil infiltration in response to recombinant C5a was examined in guinea-pig skin. 2. LTB4 (10-300 ng) and C5a (1-10 micrograms) caused a dose-dependent increase in the levels of eosinophil peroxidase activity (a measure of eosinophil infiltrati...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1994.tb16182.x
更新日期：1994-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle asse...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13782
更新日期：2017-06-01 00:00:00
abstract：UNLABELLED:Cell movement is a fundamental process of normal cellular physiology and pathophysiology. Abnormal regulation of cell migration is a common denominator of many medical disorders, including cancer metastasis, autoimmune disease and inflammation. Increased interest in the targeting of cell migration and invasi...
journal_title：British journal of pharmacology
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doi：10.1111/bph.12849
更新日期：2014-12-01 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. Changes in cutaneous water loss were followed by continuously monitoring total body weight loss.2. Sweating was induced in normal subjects by raising the environmental temperature or by subjecting them to the emotional stress of mental arithmetic.3. Propranolol in a dosage of 0.15 mg/kg body weight intravenously ha...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1973.tb08180.x
更新日期：1973-03-01 00:00:00
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
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doi：10.1111/j.1476-5381.1982.tb08775.x
更新日期：1982-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein...
journal_title：British journal of pharmacology
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更新日期：2008-09-01 00:00:00
abstract：:1. This study was undertaken to evaluate in vivo the influence of amiodarone on the effects of triiodothyronine (T3) in brown adipose tissue (BAT) which are independent of thyroid hormone synthesis and of the conversion of thyroxine (T4) to T3. Thyroidectomized rats were given a replacement dose of T3 (0.5 mg kg(-1) p...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0702456
更新日期：1999-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12956.x
更新日期：1990-03-01 00:00:00
abstract：:1. The effects of several drugs, including antagonists of vasoactive intestinal peptide (VIP), and antisera to VIP or peptide histidine isoleucine (PHI), on relaxation responses of guinea-pig isolated trachea to electrical field stimulation (EFS) have been examined. 2. beta-Adrenoceptor blockade with propranolol only ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11847.x
更新日期：1989-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb16764.x
更新日期：1981-05-01 00:00:00
abstract：:1. The current study investigated the effects of respiratory tract viral infection on the density of ETA and ETB receptors in murine tracheal smooth muscle and on the contractile response to endothelin-1 mediated by these receptors. 2. Quantitative autoradiographic studies using [125I]-endothelin-1 revealed that trach...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13209.x
更新日期：1994-08-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07536.x
更新日期：1977-08-01 00:00:00
abstract：:Adrenomedullin (AM) has two known receptors formed by the calcitonin receptor-like receptor (CL) and receptor activity-modifying protein (RAMP) 2 or 3: we report the effects of the antagonist fragments of human AM and CGRP (AM22-52 and CGRP8-37) in inhibiting AM at human (h), rat (r) and mixed species CL/RAMP2 and CL/...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705472
更新日期：2003-10-01 00:00:00
