Abstract:
:The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels (K(Ca)) has been suggested to play a critical role in initializing EDHF-dilator responses in conduit and resistance-sized arteries of many species including humans. Endothelial K(Ca) currents are mediated by the two K(Ca) subtypes, intermediate-conductance K(Ca) (KCa3.1) (also known as, a.k.a. IK(Ca)) and small-conductance K(Ca) type 3 (KCa2.3) (a.k.a. SK(Ca)). In this review, we summarize current knowledge about endothelial KCa3.1 and KCa2.3 channels, their molecular and pharmacological properties and their specific roles in endothelial function and, particularly, in the EDHF-dilator response. In addition we focus on recent experimental evidences derived from KCa3.1- and/or KCa2.3-deficient mice that exhibit severe defects in EDHF signalling and elevated blood pressures, thus highlighting the importance of the KCa3.1/KCa2.3-EDHF-dilator system for blood pressure control. Moreover, we outline differential and overlapping roles of KCa3.1 and KCa2.3 for EDHF signalling as well as for nitric oxide synthesis and discuss recent evidence for a heterogeneous (sub) cellular distribution of KCa3.1 (at endothelial projections towards the smooth muscle) and KCa2.3 (at inter-endothelial borders and caveolae), which may explain their distinct roles for endothelial function. Finally, we summarize the interrelations of altered KCa3.1/KCa2.3 and EDHF system impairments with cardiovascular disease states such as hypertension, diabetes, dyslipidemia and atherosclerosis and discuss the therapeutic potential of KCa3.1/KCa2.3 openers as novel types of blood pressure-lowering drugs.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Grgic I,Kaistha BP,Hoyer J,Köhler Rdoi
10.1111/j.1476-5381.2009.00132.xsubject
Has Abstractpub_date
2009-06-01 00:00:00pages
509-26issue
4eissn
0007-1188issn
1476-5381pii
BPH132journal_volume
157pub_type
杂志文章,评审abstract::1. In isolated Langendorff-perfused, electrically-paced, hearts of guinea-pigs, global low-flow-ischaemia (LFI; at 0.7 ml min-1) resulted in marked increases in the rates of release of lactate, lactate dehydrogenase (LDH) and creatine kinase (CK) over a 30 min period. At the end of the LFI period, tissue ATP content w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13637.x
更新日期:1993-07-01 00:00:00
abstract::The role of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) in the upper urinary tract of the guinea-pig and rat was examined using simultaneous tension recordings of the proximal and distal regions of the renal pelvis and the ureter. The guinea-pig upper urinary tract contracted at a frequency (7.52+/-0.3 min...
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abstract::Lignocaine suppresses insulin-stimulated glucose transport into the cells and insulin-stimulated glycogenesis at doses equivalent to that used in the treatment of muscle pain disorder. We evaluated the direct effect of lignocaine on insulin receptor (IR) kinase activity. After lignocaine (40 mM, approximately equivale...
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abstract:BACKGROUND AND PURPOSE:Cholecystokinin (CCK) stimulates the release of amylase and lipase from the normal pancreas. However, it is not clear to what extent this occurs in the early stages of pancreatitis induced by biliary tract obstruction in the rat and whether CCK initiates an inflammatory cascade in this condition....
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abstract::The effects of aconitine, an Aconitum alkaloid, on spontaneous inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs respectively) were investigated in the mechanically dissociated rat ventromedial hypothalamic (VMH) neurons in which native presynaptic nerve terminals remained intact. Under current-clamp co...
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journal_title:British journal of pharmacology
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abstract::1. The aim of this study was to characterize the tachykinin NK2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK2 agonist [beta Ala8]NKA(4-10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376...
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doi:10.1038/sj.bjp.0706277
更新日期:2005-08-01 00:00:00
abstract::1. Salmeterol, a novel, long-acting beta-adrenoceptor agonist, has been compared with isoprenaline and salbutamol for activity in vitro on a range of beta-adrenoceptor containing preparations from laboratory animals and man, and in vivo for bronchodilator activity in the conscious guinea-pig. 2. Salmeterol, like isopr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12486.x
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Necroptosis is a form of programmed, caspase-independent, cell death, mediated by receptor-interacting protein kinases, RIPK1 and RIPK3, and the mixed lineage kinase domain-like (MLKL). Necroptosis contributes to the pathophysiology of various inflammatory, infectious, and degenerative diseases. ...
journal_title:British journal of pharmacology
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doi:10.1111/bph.14653
更新日期:2019-06-01 00:00:00
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doi:10.1038/sj.bjp.0707180
更新日期:2007-05-01 00:00:00
abstract::1. The effect of a single injection of the monoamine oxidase inhibitor, tranylcypromine, administered intravenously (20 mg/kg) or into the lateral cerebral ventricle (5-10 mg), on hypothalamic and rectal temperature, has been investigated.2. Intravenous tranylcypromine causes a significant rise in body temperature, wh...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1970-05-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/bph.13616
更新日期:2016-12-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:British journal of pharmacology
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更新日期:1989-04-01 00:00:00
abstract::1. The binding of 2-[125I]-iodomelatonin to chicken brain membranes, and the inhibition of binding by melatonin, N-acetyltryptamine and luzindole, were examined at temperatures between 4 degrees C and 37 degrees C. 2. At all temperatures studied, the binding affinity (Kd or Ki) for 2-[125I]-iodomelatonin, melatonin (b...
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abstract::1. ATP, UTP, ADP and ADP-beta-S elicited Ca2+ -signals in cultured aortic smooth muscle cells although ADP, UDP and ADP-beta-S gave approximately 40% of the maximal response seen with ATP and UTP. Adenosine, AMP or alpha,beta-methylene-ATP had no effect. These responses were attributed to P2Y2/4 and P2Y1 receptors, wh...
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更新日期:1999-04-01 00:00:00
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更新日期:2003-05-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:1991-12-01 00:00:00
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更新日期:1986-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In small arteries, small conductance Ca²⁺-activated K⁺ channels (SK(Ca)) and intermediate conductance Ca²⁺-activated K⁺ channels (IK(Ca)) restricted to the vascular endothelium generate hyperpolarization that underpins the NO- and PGI₂-independent, endothelium-derived hyperpolarizing factor respo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2013-06-01 00:00:00
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更新日期:2003-07-01 00:00:00