Direct Effects on Airway Smooth Muscle Contractile Response Caused by Endothelin-1 in Guinea Pig Trachealis

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C. 2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed. 3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh. 4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium. 5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.

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SP-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbits: mechanism of action

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.2.428 ◽

1995 ◽

Vol 78 (2) ◽

pp. 428-432 ◽

Cited By ~ 5

Author(s):

G. N. Colasurdo ◽

J. E. Loader ◽

J. P. Graves ◽

G. L. Larsen

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Indirect Effects ◽

Contractile Response ◽

Complex Interaction ◽

Direct Effects ◽

Response Curves ◽

Cholinergic Neurotransmission ◽

The Right

We studied the mechanisms involved in the airway smooth muscle (ASM) contraction to substance P (SP) in normal (control) and allergen-sensitized (immune) rabbits as well as immune rabbits exposed to allergen via the airways (immune challenged). Cumulative concentration-response curves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segments in the absence and presence of atropine (10(-5) M) in vitro. The maximal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means +/- SE. We found no difference in the contractile response to SP between control and immune animals. ASM segments obtained from immune-challenged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contraction at 10(-4) M SP in all three groups; this effect, however, was greater in immune-challenged tissues. These findings demonstrate an increased contractile response to SP in immune-challenged animals mediated by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a complex interaction between direct effects on ASM and indirect effects through modulation of cholinergic neurotransmission.

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Effect of PAR-activation on smooth muscle contractile response of guinea-pig trachea and ileum

Inflammation Research ◽

10.1007/s00011-003-0307-4 ◽

2004 ◽

Vol 53 (0) ◽

pp. S17-S18 ◽

Cited By ~ 1

Author(s):

E. S. K. Assem ◽

B. Y. C. Wan ◽

K. H. Peh ◽

F. L. Pearce

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Contractile Response ◽

Muscle Contractile

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Neutral endopeptidase modulates endothelin-1-induced airway smooth muscle contraction in guinea-pig trachea

Regulatory Peptides ◽

10.1016/0167-0115(92)90535-3 ◽

1992 ◽

Vol 39 (2-3) ◽

pp. 137-145 ◽

Cited By ~ 17

Author(s):

Giuseppe U. Di Maria ◽

Michio Katayama ◽

D.Benjamin Borson ◽

Jay A. Nadel

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Muscle Contraction ◽

Airway Smooth Muscle ◽

Neutral Endopeptidase ◽

Smooth Muscle Contraction ◽

Endothelin 1

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Neutral endopeptidase inhibitor potentiates endothelin-1-induced airway smooth muscle contraction

Journal of Applied Physiology ◽

10.1152/jappl.1992.73.3.1108 ◽

1992 ◽

Vol 73 (3) ◽

pp. 1108-1113 ◽

Cited By ~ 14

Author(s):

T. Yamaguchi ◽

H. Kohrogi ◽

O. Kawano ◽

M. Ando ◽

S. Araki

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Airway Smooth Muscle ◽

Enzyme Inhibitor ◽

Neutral Endopeptidase ◽

Smooth Muscle Contraction ◽

Response Curves ◽

Human Bronchus ◽

Endothelin 1 ◽

C Fibers

To study the role of neutral endopeptidase (NEP) on endothelin-1-induced contraction of the airway smooth muscle, we examined the contractile effect of endothelin-1 in the isolated guinea pig trachea and human bronchus in the presence or absence of NEP inhibitor phosphoramidon. After incubation with phosphoramidon (10(-8) to 10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(-7) M to the airway tissues in organ baths. Phosphoramidon significantly potentiated the endothelin-1-induced contraction in a concentration-dependent fashion in both guinea pig trachea and human bronchus, and it shifted the concentration-response curves to the left. Because NEP is known to cleave tachykinins, we next studied whether endothelin-1 contracts airway tissues by releasing endogenous tachykinins from bronchial C-fibers. After incubation with phosphoramidon (10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(-7) M to the tissues that were treated with capsaicin to deplete the tachykinins. Phosphoramidon significantly potentiated the endothelin-1-induced contraction in the capsaicin-treated tissues, suggesting that endothelin-1 causes the contraction, at least in part, without releasing tachykinins. In contrast to the effect of phosphoramidon, captopril (an angiotensin-converting enzyme inhibitor), leupeptin (a serine protease inhibitor), and bestatin (an aminopeptidase inhibitor) did not modulate the effect of endothelin-1-induced contraction in both guinea pig trachea and human bronchus. From these results, we conclude that NEP plays an important role in regulating endothelin-1-induced contraction in the guinea pig trachea and human bronchus.

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Direct Effects of H2-Receptor Antagonists on Airway Smooth Muscle and on Responses Mediated by H1- and H2-Receptors

Anesthesiology ◽

10.1097/00000542-198702000-00012 ◽

1987 ◽

Vol 66 (2) ◽

pp. 181-185 ◽

Cited By ~ 2

Author(s):

Yoshihisa Koga ◽

Naofumi Iwatsuki ◽

Yasuhiko Hashimoto

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Direct Effects ◽

Receptor Antagonists ◽

H2 Receptor Antagonists ◽

H2 Receptor ◽

H2 Receptors

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IL-1 beta and IL-6 induce hyperplasia and hypertrophy of cultured guinea pig airway smooth muscle cells

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.4.1555 ◽

1995 ◽

Vol 78 (4) ◽

pp. 1555-1563 ◽

Cited By ~ 58

Author(s):

S. De ◽

E. T. Zelazny ◽

J. F. Souhrada ◽

M. Souhrada

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Protein Content ◽

Airway Smooth Muscle ◽

Dna Content ◽

Thymidine Incorporation ◽

Interleukin 1 ◽

Total Protein Content ◽

Leucine Incorporation ◽

Airway Smooth Muscle Cells

Guinea pig airway smooth muscle (ASM) cells were maintained in a primary tissue culture (passages 1–3). Cells were exposed to human recombinant interleukin-1 beta (IL-1 beta; 20–100 pg/ml) or interleukin-6 (IL-6; 1–4 ng/ml) in the presence of indomethacin (1 microgram/ml) for up to 5 days. Proliferation of ASM cells was assessed with two techniques, direct counting of cells with a hemacytometer and [3H]thymidine incorporation corrected for total protein content. Hypertrophy of ASM cells was assessed by [3H]leucine incorporation (evaluation of protein synthesis), determination of total DNA content, DNA content per cell, and protein content per cell. We observed that the exposure of ASM cells to human recombinant IL-1 beta or IL-6, in all studied concentrations, significantly increased the number of cells as well as [3H]thymidine incorporation into ASM cells. We also found that exposure of ASM to these two cytokines increased [3H]leucine incorporation into the ASM cells and increased protein content and DNA content per single cell. These changes were also concentration dependent. We conclude that the two proinflammatory cytokines, IL-1 beta and IL-6, which are present in asthmatic lungs, increased the proliferation of ASM cells (hyperplasia) as well as their overall size and size of their nuclei, as measured by biochemical markers. These findings are compatible with the presence of ASM hypertrophy.

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Actin reorganization in airway smooth muscle cells involves Gq and Gi-2 activation of Rho

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1999.277.3.l653 ◽

1999 ◽

Vol 277 (3) ◽

pp. L653-L661 ◽

Cited By ~ 44

Author(s):

Carol A. Hirshman ◽

Charles W. Emala

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Airway Smooth Muscle ◽

Actin Polymerization ◽

Muscle Cells ◽

Fiber Formation ◽

Airway Smooth Muscle Cells ◽

Actin Reorganization ◽

Endothelin 1 ◽

In Cells

Extracellular stimuli induce cytoskeleton reorganization (stress-fiber formation) in cells and Ca2+ sensitization in intact smooth muscle preparations by activating signaling pathways that involve Rho proteins, a subfamily of the Ras superfamily of monomeric G proteins. In airway smooth muscle, the agonists responsible for cytoskeletal reorganization via actin polymerization are poorly understood. Carbachol-, lysophosphatidic acid (LPA)-, and endothelin-1-induced increases in filamentous actin staining are indicative of actin reorganization (filamentous-to-globular actin ratios of 2.4 ± 0.3 in control cells, 6.7 ± 0.8 with carbachol, 7.2 ± 0.8 with LPA, and 7.4 ± 0.9 with endothelin-1; P < 0.001; n = 14 experiments). Although the effect of all agonists was blocked by C3 exoenzyme (inactivator of Rho), only carbachol was blocked by pertussis toxin. Although carbachol-induced actin reorganization was blocked in cells pretreated with antisense oligonucleotides directed against Gαi-2 alone, LPA- and endothelin-1-induced actin reorganization were only blocked when both Gαi-2 and Gqα were depleted. These data indicate that in human airway smooth muscle cells, carbachol induces actin reorganization via a Gαi-2pathway, whereas LPA or endothelin-1 induce actin reorganization via either a Gαi-2 or a Gqα pathway.

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