Testosterone-induced relaxation involves L-type and store-operated Ca2+ channels blockade, and PGE2 in guinea pig airway smooth muscle

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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Effect ofDesmodium adscendens fraction F1 (DAF1) on tone and agonist-induced contractions of guinea pig airway smooth muscle

Phytotherapy Research ◽

10.1002/ptr.2650030304 ◽

1989 ◽

Vol 3 (3) ◽

pp. 85-90 ◽

Cited By ~ 9

Author(s):

Marian E. Addy ◽

John F. Burka

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Airway Smooth Muscle

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Expression of dihydropyridine resistance differs in porcine bronchial and tracheal smooth muscle

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1994.267.2.l106 ◽

1994 ◽

Vol 267 (2) ◽

pp. L106-L112 ◽

Cited By ~ 2

Author(s):

T. L. Croxton ◽

C. Fleming ◽

C. A. Hirshman

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Isometric Tension ◽

Tracheal Smooth Muscle ◽

Airway Smooth Muscle Cells ◽

Channel Blockers ◽

Response Curves ◽

Voltage Dependent ◽

Relaxation Responses ◽

Ca2 Channels

Voltage-dependent and receptor-operated Ca2+ entry mechanisms have been demonstrated in airway smooth muscle, but their relative importance for maintenance of contraction is unknown. Blockade of voltage-dependent Ca2+ channels (VDC) has produced inconsistent relaxation. We postulated regional variations in Ca2+ handling by airway smooth muscle cells and compared the efficacy of dihydropyridine VDC blockers in tracheas and bronchi. Porcine tracheal smooth muscle strips and bronchial rings were mounted in tissue baths filled with physiological solutions and isometric tension was measured. Tissues were precontracted with carbachol or KCl, and relaxation dose-response curves to nifedipine, Mn2+, or Cd2+ were obtained. Relaxation responses to nifedipine were significantly different in carbachol-contracted tracheas and bronchi. Whereas carbachol-contracted tracheal muscle completely relaxed with 10(-6) M nifedipine, bronchial smooth muscle relaxed < 50%. In contrast, KCl-contracted bronchial muscle was completely relaxed by nifedipine. The nonspecific Ca2+ channel blockers Mn2+ and Cd2+ produced similar relaxation responses in each tissue. Thus VDC are the predominant mechanism for Ca2+ entry in porcine tracheal smooth muscle, but a dihydropyridine-insensitive pathway is functionally important in carbachol-contracted porcine bronchi. Regional variation may account for apparent inconsistencies between previous studies.

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Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness

Clinical Science ◽

10.1042/cs0700571 ◽

1986 ◽

Vol 70 (6) ◽

pp. 571-575 ◽

Cited By ~ 32

Author(s):

Christopher Murlas

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Airway Smooth Muscle ◽

Contractile Response ◽

Electrical Field Stimulation ◽

Physiological Salt Solution ◽

Induced Responses ◽

Field Stimulation ◽

Electrical Field ◽

Airway Mucosa

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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