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 identified as Ca(2+)-activated K(+) channel (K(Ca)) currents based on their single-channel conductance (145 pS), apparent reversal potential, and insensitivity to tolbutamide. Smaller single-channel currents with a conductance (32 pS) indicative of adenosine triphosphate-sensitive K(+) channels (K(ATP) channels) were also recorded, but were insensitive to loperamide. 3 Surprisingly, the loperamide-activated currents persisted in the absence of extracellular Ca(2+). Yet under these conditions, we still measured loperamide-induced Ca(2+) increases. These effects are dose dependent. Loperamide had no effects in the inside-out patch configuration, suggesting that loperamide does not directly activate the channels with large conductance, but does so secondarily to release of Ca(2+) from intracellular stores. 4 Carbachol (100 micro M), an agonist of muscarinic receptors, which mediates IP(3)-dependent intracellular Ca(2+) release, enhanced the effects of loperamide on K(Ca) channels. 5 Both the putative K(Ca) currents and Ca(2+) signals induced by loperamide (with '0' [Ca(2+)](o)) were abolished when the intracellular Ca(2+) stores had been emptied by pretreating the cells with either carbachol or thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor that blocks reuptake of calcium. 6 These data indicate that loperamide in insulin-secreting beta-cells evokes intracellular Ca(2+) release from IP(3)-gated stores and activates membrane currents that appear to be carried by K(Ca), rather than K(ATP) channels.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
He LP,Mears D,Atwater I,Rojas E,Cleemann Ldoi
10.1038/sj.bjp.0705263subject
Has Abstractpub_date
2003-05-01 00:00:00pages
351-61issue
2eissn
0007-1188issn
1476-5381journal_volume
139pub_type
杂志文章abstract：:1. 5-Hydroxytryptamine (5-HT) stimulates active sodium transport and decreases the passive mucosal to serosal chloride permeability across frog skin. The relative importance of the different regions of the 5-HT molecule in the mediation of these responses has been studied using a range of structurally related compound...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb07867.x
更新日期：1979-04-01 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
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707180
更新日期：2007-05-01 00:00:00
abstract：:The effect of bath-applied luteinizing hormone-releasing factor (LHRF) was recorded in voltage-clamped bullfrog lumbar sympathetic neurones. At a holding potential of -- 30 mV, LHRF induced a steady inward (depolarizing) current and reduced membrane conductance; at -- 60 mV LHRF produced negligible inward current and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb14547.x
更新日期：1980-03-01 00:00:00
abstract：:1. This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2. Systemic administration of low doses of endotoxin (40 microg kg(-1), i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3. Funct...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704258
更新日期：2001-09-01 00:00:00
abstract：:1. Muscularis mucosae of the distal oesophagus of the opossum contracts in response to substance P and to a variety of tachykinins. To delineate the nature of the receptors present in this tissue, we evaluated contractile responses to substance P, neurokinin A, neurokinin B, eledoisin and analogues believed to be high...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12556.x
更新日期：1989-08-01 00:00:00
abstract：:1. The goal of this study was to determine if an increase in cytoplasmic calcium concentration ([Ca2+]i), in the absence of additional second messengers derived from membrane phospholipid turnover, is a sufficient signal to induce chloride secretion across monolayers of the human colonic epithelial line, T84. 2. Thaps...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1993.tb13599.x
更新日期：1993-06-01 00:00:00
abstract：:1. Voltage-operated calcium channel (VOCC) antagonists are effective antihypertensive and antianginal agents but they also depress myocardial contractility. 2. We compared four L-type calcium channel antagonists, felodipine, nifedipine, amlodipine and verapamil and a relatively T-type selective calcium channel antagon...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702045
更新日期：1998-09-01 00:00:00
abstract：:Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703623
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb09934.x
更新日期：1971-01-01 00:00:00
abstract：:1 Effects of dopamine and noradrenaline were compared in helically-cut strips of canine cerebral arteries. 2 Dopamine caused a greater maximal contraction than noradrenaline, although the ED50 for noradrenaline was appreciably less. The contraction induced by these amines was reversed to a relaxation by treatment with...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07700.x
更新日期：1976-09-01 00:00:00
abstract：:1. A comparative study was carried out to assess the regional haemodynamic effects of intravenous infusion of human alpha- and beta-calcitonin gene-related peptide (CGRP; 0.006, 0.06 and 0.6 nmol h-1) in conscious, unrestrained Wistar rats. 2. With human alpha-CGRP, tachycardia was always accompanied by a fall in mean...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12668.x
更新日期：1989-12-01 00:00:00
abstract：:1. The aim of this study was to assess the role of endothelial cells in the modulation of vasocontractile responses to endothelin-1 (ET-1) of human placental vasculature. 2. Isolated stem villi small arteries (diameter = 170-250 microns) were obtained from healthy parturients who underwent caesarean surgery during the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15915.x
更新日期：1995-07-01 00:00:00
abstract：:1 alpha-Monofluoromethyldopa (MFMD, RMI 71963), a potent and selective enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase produces a substantial and long-lasting decrease in the catecholamine content of mouse brain, heart and kidney. 2 Single doses of MFMD reduce the 5-hydroxytryptamine con...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb09776.x
更新日期：1980-12-01 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. The effects of pregnancy on mesenteric arterial function were examined in constantly perfused (5 ml min-1) mesenteric arterial beds isolated from 21-day pregnant rats. The function of sympathetic and sensory-motor perivascular nerves, endothelium and smooth muscle was examined. The role of nitric oxide and prostagl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15307.x
更新日期：1996-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Translation of non-clinical markers of delayed ventricular repolarization to clinical prolongation of the QT interval corrected for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. We retrospectively analysed 150 d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14101
更新日期：2018-02-01 00:00:00
abstract：:1. Although extensively investigated, the extent of differences between receptors mediating negative inotropic and chronotropic responses is still unclear. In the present study atrial and intestinal muscarinic receptors were identified by [3H]-N-methyl-scopolamine ([3H]-NMS) binding and the affinities of some presumab...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11987.x
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abstract：:The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found t...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1987.tb08990.x
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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
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doi：10.1111/j.1476-5381.1977.tb08421.x
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abstract：:1. The irritant fungal terpenoid isovelleral caused protective eye-wiping movements in the rat upon intraocular instillation and showed cross-tachyphylaxis with capsaicin, the pungent principle in hot pepper. 2. Isovelleral induced a dose-dependent calcium uptake by rat dorsal root ganglion neurones cultured in vitro ...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1996.tb15983.x
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abstract：BACKGROUND AND PURPOSE:Pancreatic cancer is characterized by alterations in several key signalling proteins, including increased expression and activity of the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked to its chemoresistance. Sustained Src inhibition reactivates survival pathways regul...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12855
更新日期：2015-01-01 00:00:00
abstract：:1. Our study was aimed at investigating the duration of the bronchodilator action of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium. In the guinea-pig isolated trachea, the time (t1/2) necessary for a contractile response to carbachol (0.3 microM) to return to 50% recovery after washout o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706724
更新日期：2006-06-01 00:00:00
abstract：:1. Prostaglandins and the vasodilator neuropeptide, calcitonin-gene related peptide (CGRP), have both been implicated in the pathogenesis of migraine headache. We have used primary cultures of adult rat trigeminal neurones to examine the effects of prostanoids on CGRP release in vitro. 2. CGRP release was stimulated b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704357
更新日期：2001-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium-derived nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00348.x
更新日期：2009-09-01 00:00:00
abstract：:1. We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT1-like- and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15188.x
更新日期：1996-01-01 00:00:00
abstract：:1 A newly synthesized substance P (SP) analogue, (D-Pro2, D-Trp7,9)-SP, specifically antagonizes the contractile effects of SP on the guinea-pig isolated taenia coli. In addition, previous studies had indicated that the SP analogue per se is capable of contracting this preparation. The results of the present study on ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09348.x
更新日期：1982-12-01 00:00:00
abstract：:1. We assessed the relaxant effect of 17 beta-oestradiol (10(-7), 10(-6) and 10(-5) M) on rabbit isolated coronary arteries precontracted with prostaglandin F2 alpha (3 x 10(-6) M), high extracellular potassium (30 mM) and Bay K 8644 (10(-6) M) plus high extracellular potassium (15 mM) by measuring isometric tension. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12545.x
更新日期：1991-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12509
更新日期：2014-02-01 00:00:00
abstract：:1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor. Here we describe the in vitro and in vivo pharmacological profile of a novel NOP receptor ligand, [Nphe(1)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704706
更新日期：2002-05-01 00:00:00
abstract：:1. The present study addressed the role of neuropeptide (NPY) Y2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Wester...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706774
更新日期：2006-07-01 00:00:00
