ArticleRespiratory research2006
Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor.
Article in Respiratory research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 120 citations in OpenAlex.
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- Secretin targets interstitial cells of Cajal to regulate intestinal contractions.EMBO reports · 2025Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Testosterone Enhances KInternational journal of molecular sciences · 2024Article
- Theophylline-Induced Relaxation Is Enhanced after Testosterone Treatment via Increased KInternational journal of molecular sciences · 2023Article
- Perspectives on precision cut lung slices-powerful tools for investigation of mechanisms and therapeutic targets in lung diseases.Frontiers in pharmacology · 2023Review
- Imidazobenzodiazepine PI320 Relaxes Mouse Peripheral Airways by Inhibiting Calcium Mobilization.American journal of respiratory cell and molecular biology · 2022Article
- Investigation of effects of fluoxetine on the bronchial smooth muscles by the isolated organ bath system.Biologia futura · 2022Article
- STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Opening up to cAMP Transport Mechanisms in Airway Smooth Muscle.American journal of respiratory cell and molecular biology · 2022Article
- Bile acids inhibit cholinergic constriction in proximal and peripheral airways from humans and rodents.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle.Scientific reports · 2018Article
- Article
- Epithelial Cells Induce a Cyclo-Oxygenase-1-Dependent Endogenous Reduction in Airway Smooth Muscle Contractile Phenotype.American journal of respiratory cell and molecular biology · 2017Article
- Prostaglandin EMolecular pharmacology · 2017Article
- The relative contributions of store-operated and voltage-gated CaThe Journal of physiology · 2017Article
- Store-operated calcium entry is required for sustained contraction and CaThe Journal of physiology · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.American journal of respiratory cell and molecular biology · 2016Article
- Cortex phellodendri Extract Relaxes Airway Smooth Muscle.Evidence-based complementary and alternative medicine : eCAM · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIt has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca2+ oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca2+ oscillations.
methodsThe effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca2+ signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy.
resultsAll three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca2+ oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca2+ oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca2+ oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca2+ stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca2+ available to stimulate contraction because an elevation of intracellular Ca2+ concentration induced by exposure to a Ca2+ ionophore (ionomycin) or by photolysis of caged-Ca2+ did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca2+-activated K+ channels, which would be expected to increase Ca2+ influx and contraction. By contrast, the photolysis of caged-IP3 in the presence of agonist, to further elevate the intracellular IP3 concentration, reversed the slowing of the frequency of the Ca2+ oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP3R to IP3 was reduced by FSK and this was supported by the reduced ability of IP3 to release Ca2+ in SMCs in the presence of FSK.
conclusionThese results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca2+ oscillation frequency by reducing internal Ca2+ release through IP3 receptors.
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