ArticleBritish journal of pharmacology2001
Mechanisms of leukotriene D4-induced constriction in human small bronchioles.
Article in British journal of pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 42 citations in OpenAlex.
- Cysteinyl Leukotriene Pathway and Cancer.International journal of molecular sciences · 2021Review
- RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets.Clinical & translational immunology · 2020Review
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
- Reduction of Asthmatic Parameters by Sea Hare Hydrolysates in a Mouse Model of Allergic Asthma.Nutrients · 2017Article
- The CatSper channel: a polymodal chemosensor in human sperm.The EMBO journal · 2012Article
- Methylmercury-induced IL-6 release requires phospholipase C activities.Neuroscience letters · 2011Article
- Molecular expression and functional role of canonical transient receptor potential channels in airway smooth muscle cells.Advances in experimental medicine and biology · 2011Review
- Functional role of canonical transient receptor potential 1 and canonical transient receptor potential 3 in normal and asthmatic airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2010Article
- Ion transport regulated by protease-activated receptor 2 in human airway Calu-3 epithelia.British journal of pharmacology · 2005Article
- TRP channels in airway smooth muscle as therapeutic targets.Naunyn-Schmiedeberg's archives of pharmacology · 2005Review
- Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
We examined the mechanisms underlying leukotriene D4- (LTD4) induced constriction of human small (300 - 500 micron i.d.) bronchioles, and the effect of LTD4 on ion currents and Ca2+ transients in smooth muscle cells (SMC) isolated from these bronchioles. LTD4 caused a concentration-dependent bronchoconstriction with an EC50=0.58+/-0.05 nM (n=7) which was not easily reversible upon washout. This bronchoconstriction was entirely dependent on extracellular Ca2+. Blockade of L-type Ca2+ channels with nifedipine (10 microM) reduced LTD4 response by 39+/-2% (n=8), whilst La3+, Gd3+ and SK&F 96,365 abolished LTD4-induced bronchoconstriction completely and reversibly, suggesting the majority of Ca2+ entry was via non-selective cation channels. Antagonists of PI-PLC (U73,122 and ET-18-OCH3), PLD (propranolol) and PKC (cheleretrine and Ro31-8220) were without any effect on LTD4-induced bronchoconstriction, whilst the PC-PLC inhibitor D609 caused complete relaxation. Inhibition of protein tyrosine kinase with tyrphostin A23 (100 microM) caused about 50% relaxation, although the inactive analogue tyrphostin A1 was without effect. In freshly isolated SMC from human small bronchioles LTD4 caused a slow increase of intracellular Ca2+ concentration, with a consequent rise of the activity of large conductance Ca2+-dependent K+ channels and the amplitude of depolarization-induced outward whole-cell current. Again, no effect of LTD4 could be observed in the absence of extracellular Ca2+. We conclude that LTD4 causes constriction of these small bronchioles primarily by activating Ca2+ entry via non-voltage gated channels, possibly by a PC-PLC mediated pathway.
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