A smooth muscle tone-dependent stretch-activated migrating motor pattern in isolated guinea-pig distal colon

Airway levels of the endogenous bronchodilator S-nitrosoglutathione (GSNO) are low in children with near-fatal asthma. We hypothesized that GSNO could be broken down in the lung and that this catabolism could inhibit airway smooth muscle relaxation. In our experiments, GSNO was broken down by guinea pig lung homogenates, particularly after ovalbumin sensitization (OS). Two lung protein fractions had catabolic activity. One was NADPH dependent and was more active after OS. The other was NADPH independent and was partially inhibited by aurothioglucose. Guinea pig lung tissue protein fractions with GSNO catabolic activity inhibited GSNO-mediated guinea pig tracheal ring relaxation. The relaxant effect of GSNO was partially restored by aurothioglucose. These observations suggest that catabolism of GSNO in the guinea pig 1) is mediated by lung proteins, 2) is partially upregulated after OS, and 3) may contribute to increased airway smooth muscle tone. We speculate that enzymatic breakdown of GSNO in the lung could contribute to asthma pathophysiology by inhibiting the beneficial effects of GSNO, including its effect on airway smooth muscle tone.

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An in vivo guinea pig preparation for studying the autonomic regulation of airway smooth muscle tone

Autonomic Neuroscience ◽

10.1016/s1566-0702(02)00053-x ◽

2002 ◽

Vol 99 (2) ◽

pp. 91-101 ◽

Cited By ~ 18

Author(s):

Stuart B Mazzone ◽

Brendan J Canning

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Airway Smooth Muscle ◽

Muscle Tone ◽

Autonomic Regulation ◽

Smooth Muscle Tone

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Melatonin MT2 receptor is expressed and potentiates contraction in human airway smooth muscle

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00273.2021 ◽

2021 ◽

Author(s):

Haruka Sasaki ◽

Yi Zhang ◽

Charles W Emala ◽

Kentaro Mizuta

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Airway Smooth Muscle ◽

Muscle Tone ◽

Fiber Formation ◽

Melatonin Receptors ◽

Human Airway Smooth Muscle ◽

Nocturnal Asthma ◽

Smooth Muscle Tone ◽

Human Airway

Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor which couples to both Gq and Gi proteins, and the MT2 receptor which couples to Gi. We investigated whether melatonin receptors are expressed on airway smooth muscle, whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca2+]i) which modulate airway smooth muscle tone, and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblotting, and immunohistochemistry. Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10 - 100 µM) or the non-selective MT1/MT2 agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated cAMP accumulation in HASM cells, which was reversed by the Gαi protein inhibitor pertussis toxin or knockdown of the MT2 receptor by its specific siRNA. Although melatonin by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin significantly potentiated acetylcholine-stimulated [Ca2+]i increases, stress fiber formation through the MT2 receptor in HASM cells, and attenuated the relaxant effect of isoproterenol in guinea pig trachea. These findings suggest that the melatonin MT2 receptor is expressed in ASM, and modulates airway smooth muscle tone via reduced cAMP production and increased [Ca2+]i.

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