Inhaled corticosteroids inhibit substance P receptor expression in asthmatic rat airway smooth muscle cells

Cultured airway smooth muscle cells provide a convenient model system for studying the regulation of a wide range of airway responses at the cellular level. This review describes the characteristics of cultured airway smooth muscle cells and differences that exist between cultured cells and acutely dissociated cells or muscle strips. Receptor and ion-channel expression and control of coupling in cultured airway smooth muscle are reviewed. The methodology for airway smooth muscle culture is discussed. The main advantage of using cultured airway smooth muscle cells is that studies can be performed to examine long-term control of cell responses. Studies of the regulation of receptor expression and coupling, desensitization of receptor or channel-mediated responses, or regulation of the expression of important enzymes or muscle proteins can be readily performed in cell culture. In addition, cultured airway myocytes provide a useful secondary screening system for the development of novel therapeutic agents targeted at airway receptors that are expressed upon these cells.

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Fcε Receptor Expression in Human Airway Smooth Muscle Cells

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb.46.4.560 ◽

2012 ◽

Vol 46 (4) ◽

pp. 560-560

Author(s):

YuXiu C. Xia ◽

Alastair G. Stewart ◽

Graham A. Mackay ◽

Malcolm Shepherd ◽

William T. Gerthoffer ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Receptor Expression ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway

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ET-1 induces mitogenesis in ovine airway smooth muscle cells via ETA and ETB receptors

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.5.l1021 ◽

1997 ◽

Vol 272 (5) ◽

pp. L1021-L1024

Author(s):

P. Carratu ◽

M. Scuri ◽

J. L. Styblo ◽

A. Wanner ◽

M. K. Glassberg

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Receptor Expression ◽

Airway Smooth Muscle Cells ◽

Receptor Subtypes ◽

Dependent Manner ◽

Bq 610 ◽

20 Nm

The proliferation of airway smooth muscle cells is a characteristic feature of asthma. Endothelin (ET)-1, a member of a family of three isopeptides (ET-1, ET-2, and ET-3), functions as a spasmogen and mitogen for airway smooth muscle cells. Two types of ET receptors have been identified in mammalian species (ETA and ETB). Because the respective roles of ETA and ETB receptors in ET-1-induced mitogenesis are not known, we determined the effect of two selective ETA and ETB antagonists (BQ-610 and BQ-788) on ET-1-induced mitogenesis of cultured ovine airway smooth muscle cells. Both BQ-610 and BQ-788 inhibited ET-1-induced mitogenesis in a concentration-dependent manner, with BQ-788 exhibiting more potent antagonism [half-maximal inhibitory concentration (IC50) = 3.5 nM, slope of 0.49] compared with BQ-610 (IC50 = 20 nM, slope of 0.27). The combined ETA-ETB antagonist, bosentan, also inhibited ET-1-induced mitogenesis (IC50 = 20 nM, slope of 0.60). The effects of BQ-788 and bosentan appear to be mediated via the same receptor (ETB), as their slopes are comparable. These observations suggest that both receptor subtypes are utilized in ET-1-induced proliferation of ovine airway smooth muscle. ET receptor expression may be important in the increase in airway smooth muscle mass seen in the airways of patients with bronchial asthma.

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Substance P activates Cl− and K+ conductances in guinea-pig tracheal smooth muscle cells

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-100 ◽

1994 ◽

Vol 72 (6) ◽

pp. 705-710 ◽

Cited By ~ 16

Author(s):

Luke J. Janssen ◽

Stephen M. Sims

Keyword(s):

Smooth Muscle ◽

Substance P ◽

Guinea Pig ◽

Smooth Muscle Cells ◽

Voltage Clamp ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Equilibrium Potential ◽

Airway Smooth Muscle Cells ◽

Inward Current

Substance P (SP) causes bronchoconstriction, but its effects on airway smooth muscle ion conductances are unknown. We investigated the effects of SP on single smooth muscle cells dissociated from guinea-pig trachealis. Under voltage clamp at −60 mV, SP evoked reversible contractions and inward current (ISP). ISP had a latency of approximately 1 s, reached a peak of 1039 ± 147 pA (n = 19) about 2 s after onset of application, and declined to baseline levels over the next 5–10 s. At more positive holding potentials (−25 and 0 mV), the inward current was decreased in magnitude and preceded by outward current. With 140 mM K+ in the electrode and Cl− equilibrium potential (ECl) of about 0 mV, ISP was outwardly rectifying and reversed at −11 ± 2 mV. When K+ currents were blocked using Cs+, the current–voltage relationship for ISP was linear and reversed at 3 ± 1 mV. The reversal potential was dependent on the Cl− gradient across the membrane. These results suggest that SP caused a transient activation of Cl− and K+ conductances. Following the initial transient inward current, SP caused a prolonged suppression of spontaneously active K+ currents. The findings that SP evoked contractions during voltage clamp at potentials at which voltage-dependent Ca2+ channels are not active, and that current oscillations were also evoked by SP, suggest that SP is acting through release of Ca2+ from internal stores. Furthermore, SP occluded the inward current evoked by acetylcholine, suggesting that the peptidergic and cholinergic signalling pathways converge. We conclude that SP releases Ca2+ from internal stores in guinea-pig airway smooth muscle cells, leading to activation of Cl− and K+ conductances, depolarization, and contraction.Key words: Ca2+-dependent conductances, spontaneous transient outward currents, acetylcholine.

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