Respiratory epithelium modulates the responses of canine bronchi to cooling

1993 ◽  
Vol 74 (5) ◽  
pp. 2421-2425 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Nordihydroguaiaretic Acid ◽  
Respiratory Epithelium ◽  
Resting Tension ◽  
Cytochrome P 450 ◽  
Evoked Contractions

The present study was designed to investigate the effect of cooling on the modulatory role of the respiratory epithelium on the underlying smooth muscle. Canine bronchial rings and segments (with or without epithelium) were suspended in organ chambers and perfused with modified Krebs-Ringer bicarbonate solution, respectively. Isometric force was recorded. Cooling did not affect the resting tension of the bronchi. During contractions to carbachol, cooling evoked contractions in bronchi with epithelium but relaxations in those without epithelium. In the presence of indomethacin, cooling induced contractions in both preparations with and without epithelium. The contractions in bronchi with epithelium were significantly larger than those in bronchi without epithelium. After treatment with indomethacin, exogenous arachidonic acid potentiated the cooling-induced contractions in preparations with epithelium but not in those without epithelium. This potentiation was not affected by nordihydroguaiaretic acid. SKF 525-A and metyrapone, inhibitors of cytochrome P-450 monooxygenases, converted the cooling-induced contractions of preparations with epithelium to relaxations and had no significant effects on the responses of preparations without epithelium. These observations suggest that cooling induces from the epithelium the release of a cytochrome P-450-derived eicosanoid that potentiates contractions of the underlying airway smooth muscle to carbachol.

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation

1997 ◽  
Vol 83 (3) ◽  
pp. 739-745 ◽  
Author(s):  
X. Shen ◽  
M. F. Wu ◽  
R. S. Tepper ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Mechanical Response ◽  
Isometric Force ◽  
Shortening Velocity ◽  
Airway Reactivity ◽  
Pharmacological Modulation ◽  
Activation Mechanisms ◽  
Cross Bridges

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation. J. Appl. Physiol. 83(3): 739–745, 1997.—Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studied the effects of different pharmacological stimuli on airway smooth muscle to determine whether the muscle behavior during length oscillation can be modulated pharmacologically and to evaluate the role of different activation mechanisms in determining its behavior during the oscillation. Active force decreased below the static isometric force during the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic shortening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length oscillation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.

Respiratory epithelium-dependent inhibition of protein kinase C of airway smooth muscle cells

1991 ◽  
Vol 70 (5) ◽  
pp. 2137-2144 ◽  
Author(s):  
M. Souhrada ◽  
J. F. Souhrada
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Respiratory Epithelium ◽  
Resting Membrane Potential ◽  
Induced Response ◽  
Kinase C

We have examined the effect of phorbol myristate acetate (PMA) on airway smooth muscle (ASM) in the presence and absence of respiratory epithelium (RE) and analyzed the dependence of this response on extracellular sodium, Na+/H+ exchange, calcium, and cyclooxygenase products; we determined both the resting membrane potential and isometric force developed by ASM preparations. Removal of RE had no effect on the values of the resting membrane potential of ASM cells. In the presence of RE in the preparation, both electrical and contractile responses to PMA (10(-5) M) were significantly different compared with the response of ASM to PMA without RE. When the RE was present, stimulation of protein kinase C caused only a biphasic response in both membrane potential and isometric force. In either the presence or absence of RE, amiloride (10(-5) M) and a low-sodium solution inhibited both electrical and contractile changes of ASM cells caused by PMA. In the presence or absence of RE, verapamil (10(-5) M) attenuated (P less than 0.05) both electrical and contractile responses of ASM cells as induced by PMA. Verapamil, however, had no effect on the last phase of PMA-induced response. Pretreatment of preparations with indomethacin (10(-6) M) changed the PMA-induced response of ASM with RE to a response usually observed in ASM without RE. Finally, the incubation of tracheal preparations without RE with prostaglandin E2 (10(-8) M) altered the response of these preparations in such a way that their electrical and contractile response to PMA was essentially identical to the PMA response observed in preparations with an intact RE.(ABSTRACT TRUNCATED AT 250 WORDS)

Caveolae facilitate muscarinic receptor-mediated intracellular Ca2+ mobilization and contraction in airway smooth muscle

2007 ◽  
Vol 293 (6) ◽  
pp. L1406-L1418 ◽  
Author(s):  
Reinoud Gosens ◽  
Gerald L. Stelmack ◽  
Gordon Dueck ◽  
Mark M. Mutawe ◽  
Martha Hinton ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Signaling Proteins ◽  
Muscarinic Agonist ◽  
Caveolin 1 ◽  
Intracellular Ca ◽  
Domain Peptide

Contractile responses of airway smooth muscle (ASM) determine airway resistance in health and disease. Caveolae microdomains in the plasma membrane are marked by caveolin proteins and are abundant in contractile smooth muscle in association with nanospaces involved in Ca2+ homeostasis. Caveolin-1 can modulate localization and activity of signaling proteins, including trimeric G proteins, via a scaffolding domain. We investigated the role of caveolae in contraction and intracellular Ca2+ ([Ca2+]i) mobilization of ASM induced by the physiological muscarinic receptor agonist, acetylcholine (ACh). Human and canine ASM tissues and cells predominantly express caveolin-1. Muscarinic M3 receptors (M3R) and Gαq/11 cofractionate with caveolin-1-rich membranes of ASM tissue. Caveolae disruption with β-cyclodextrin in canine tracheal strips reduced sensitivity but not maximum isometric force induced by ACh. In fura-2-loaded canine and human ASM cells, exposure to methyl-β-cyclodextrin (mβCD) reduced sensitivity but not maximum [Ca2+]i induced by ACh. In contrast, both parameters were reduced for the partial muscarinic agonist, pilocarpine. Fluorescence microscopy revealed that mβCD disrupted the colocalization of caveolae-1 and M3R, but [ N-methyl-3H]scopolamine receptor-binding assay revealed no effect on muscarinic receptor availability or affinity. To dissect the role of caveolin-1 in ACh-induced [Ca2+]i flux, we disrupted its binding to signaling proteins using either a cell-permeable caveolin-1 scaffolding domain peptide mimetic or by small interfering RNA knockdown. Similar to the effects of mβCD, direct targeting of caveolin-1 reduced sensitivity to ACh, but maximum [Ca2+]i mobilization was unaffected. These results indicate caveolae and caveolin-1 facilitate [Ca2+]i mobilization leading to ASM contraction induced by submaximal concentrations of ACh.

Epithelium acts as a modulator and a diffusion barrier in the responses of canine airway smooth muscle

1994 ◽  
Vol 76 (5) ◽  
pp. 1843-1847 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Diffusion Barrier ◽  
Respiratory Epithelium ◽  
Isometric Tension ◽  
High Potassium

The present study was designed to determine the role of the respiratory epithelium as a diffusion barrier and a modulator of the responsiveness of airway smooth muscle to bronchoactive agents. Segments of canine bronchi, with or without epithelium, were suspended in organ chambers and perfused intraluminally. The isometric tension was recorded. Acetylcholine, given intraluminally, induced significantly smaller contractions in bronchi with than in bronchi without epithelium. When this agonist was given extraluminally, no difference in contractions was noted between the tissues. In the presence of acetylcholine and phentolamine, norepinephrine, given either intra- or extraluminally, induced significantly larger relaxations in bronchi with than in bronchi without epithelium. High potassium given intraluminally induced contractions only in bronchi without epithelium; however, in the presence of ouabain, both tissues contracted similarly. When high potassium was given extraluminally, no difference in contraction between tissues with and without epithelium was noted. When [3H]acetylcholine and [3H]norepinephrine were perfused intraluminally, the accumulation of 3H radioactivity in the extraluminal solutions was significantly less in bronchi with than in bronchi without epithelium. These observations suggest that the epithelium acts as both a diffusion barrier and a modulator of the responses of canine airways to bronchoactive agents.

PGE2 release by bradykinin in human airway smooth muscle cells: involvement of cyclooxygenase-2 induction

1997 ◽  
Vol 273 (6) ◽  
pp. L1132-L1140 ◽  
Author(s):  
Linhua Pang ◽  
Alan J. Knox
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Arachidonic Acid Release ◽  
Human Airway Smooth Muscle ◽  
Short Term ◽  
Human Airway ◽  
Acid Release ◽  
Cox 2

Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-term effect, whereas B2 receptor-related COX-2 induction is important in the long-term PGE2 release.

Silver nanoparticles Induce Anti-Proliferative Effects on Airway Smooth Muscle Cells. Role of Nitric Oxide and Muscarinic Receptor Signaling Pathway

2013 ◽  
Vol 65 ◽  
pp. S104
Author(s):  
Manuel Alejandro Ramirez-Lee ◽  
Hector Rosas-Hernandez ◽  
Samuel Salazar-Garcia ◽  
Jose Manuel Gutiérrez-Hernández ◽  
Ricardo Espinosa- Tanguma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Silver Nanoparticles ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Receptor Signaling Pathway

Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteries to arachidonic acid

1993 ◽  
Vol 264 (2) ◽  
pp. H327-H335 ◽  
Author(s):  
M. Rosolowsky ◽  
W. B. Campbell
Keyword(s):  
Arachidonic Acid ◽  
Coronary Arteries ◽  
Vascular Tone ◽  
Epoxyeicosatrienoic Acids ◽  
Lipoxygenase Inhibitor ◽  
Physiological Processes ◽  
Coronary Vascular Tone ◽  
Cytochrome P 450 ◽  
Endothelium Dependent Relaxation

Metabolites of arachidonic acid regulate several physiological processes, including vascular tone. The purpose of this study was to determine which metabolites of arachidonic acid are produced by bovine coronary arteries and which may regulate coronary vascular tone. Arachidonic acid induced a concentration-related, endothelium-dependent relaxation [one-half maximum effective concentration (EC50) of 2 x 10(-7) M and a maximal relaxation of 91 +/- 2% at 10(-5) M] of bovine coronary arteries that were contracted with U-46619, a thromboxane mimetic. The concentration of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of prostaglandin I2 (PGI2), increased from 82 +/- 6 to 328 +/- 24 pg/ml with arachidonic acid (10(-5) M). Treatment with the cyclooxygenase inhibitor indomethacin attenuated arachidonic acid-induced relaxations by approximately 50% and blocked the synthesis of 6-keto-PGF1 alpha. PGI2 caused a concentration-related relaxation (EC50 of 10(-8) M and a maximal relaxation of 125 +/- 11% at 10(-7) M). BW755C, a cyclooxygenase and lipoxygenase inhibitor, inhibited arachidonic acid-induced relaxation to the same extent as indomethacin. When vessels were treated with both indomethacin and BW755C, the inhibition of relaxation was the same as either inhibitor alone. SKF 525a, a cytochrome P-450 inhibitor, reduced arachidonic acid-induced relaxation by approximately 50%. When SKF 525a was given in combination with indomethacin, the relaxation by arachidonic acid was almost completely inhibited. SKF 525a inhibited the synthesis of epoxyeicosatrienoic acids (EETs).(ABSTRACT TRUNCATED AT 250 WORDS)

Myosin thick filament lability induced by mechanical strain in airway smooth muscle

2001 ◽  
Vol 90 (5) ◽  
pp. 1811-1816 ◽  
Author(s):  
Kuo-Hsing Kuo ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Lincoln E. Ford ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cross Sections ◽  
Structural Changes ◽  
Isometric Force ◽  
Mechanical Strain ◽  
Thick Filament ◽  
Functional Changes ◽  
Thick Filaments ◽  
Length Changes

Airway smooth muscle adapts to different lengths with functional changes that suggest plastic alterations in the filament lattice. To look for structural changes that might be associated with this plasticity, we studied the relationship between isometric force generation and myosin thick filament density in cell cross sections, measured by electron microscope, after length oscillations applied to the relaxed porcine trachealis muscle. Muscles were stimulated regularly for 12 s every 5 min. Between two stimulations, the muscles were submitted to repeated passive ±30% length changes. This caused tetanic force and thick-filament density to fall by 21 and 27%, respectively. However, in subsequent tetani, both force and filament density recovered to preoscillation levels. These findings indicate that thick filaments in airway smooth muscle are labile, depolymerization of the myosin filaments can be induced by mechanical strain, and repolymerization of the thick filaments underlies force recovery after the oscillation. This thick-filament lability would greatly facilitate plastic changes of lattice length and explain why airway smooth muscle is able to function over a large length range.

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