Studies on the mechanism of drug-induced bronchiolar relaxation in the guinea pig

Mn, Blumenthal; Brody, Theodore M.

doi:10.1016/0021-8707(69)90001-x

Cited by 16 publications

(4 citation statements)

References 8 publications

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“…Under our conditions, glucagon inhibited the carbachol-induced contractile response of tracheas in mice. These findings are in line with those of Blumenthal & Brody (1969), in which glucagon relaxed the bronchial smooth muscle in guinea pigs. In addition, vasoactive intestinalpeptide and pituitary adenylyl cyclase-activating polypeptide, which are peptides that have high homology with glucagon amino acid sequence (Mentlein 2009), also have the ability to relax ASMs in vitro (Sherman et al 1988, Melanson et al 1998.…”

Section: Discussionsupporting

confidence: 92%

Glucagon induces airway smooth muscle relaxation by nitric oxide and prostaglandin E2

Insuela¹,

Daleprane²,

Coelho³

et al. 2015

Journal of Endocrinology

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Glucagon is a hyperglycemic pancreatic hormone that has been shown to provide a beneficial effect against asthmatic bronchospasm. We investigated the role of this hormone on airway smooth muscle contraction and lung inflammation using both in vitro and in vivo approaches. The action of glucagon on mouse cholinergic tracheal contraction was studied in a conventional organ bath system, and its effect on airway obstruction was also investigated using the whole-body pletysmographic technique in mice. We also tested the effect of glucagon on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and inflammation. The expression of glucagon receptor (GcgR), CREB, phospho-CREB, nitric oxide synthase (NOS)-3, pNOS-3 and cyclooxygenase (COX)-1 was evaluated by western blot, while prostaglandin E 2 (PGE 2 ) and tumour necrosis factor-a were quantified by enzyme-linked immunoassay and ELISA respectively. Glucagon partially inhibited carbacholinduced tracheal contraction in a mechanism clearly sensitive to des-His1-[Glu9]-glucagon amide, a GcgR antagonist. Remarkably, GcgR was more expressed in the lung and trachea with intact epithelium than in the epithelium-denuded trachea. In addition, the glucagon-mediated impairment of carbachol-induced contraction was prevented by either removing epithelial cells or blocking NOS (L-NAME), COX (indomethacin) or COX-1 (SC-560). In contrast, inhibitors of either heme oxygenase or COX-2 were inactive. Intranasal instillation of glucagon inhibited methacholine-induced airway obstruction by a mechanism sensitive to pretreatment with L-NAME, indomethacin and SC-560. Glucagon induced CREB and NOS-3 phosphorylation and increased PGE 2 levels in the lung tissue without altering COX-1 expression. Glucagon also inhibited LPS-induced AHR and bronchoalveolar inflammation. These findings suggest that glucagon possesses airway-relaxing properties that are mediated by epithelium-NOS-3-NO-and COX-1-PGE 2 -dependent mechanisms.

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Section: Discussionsupporting

confidence: 92%

Glucagon induces airway smooth muscle relaxation by nitric oxide and prostaglandin E2

Insuela¹,

Daleprane²,

Coelho³

et al. 2015

Journal of Endocrinology

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“…Thus Bueding et al [1966] determined cyclic AMP in guinea-pig Taenia coli within 7-15 sec of applying a relaxant dose of adrenaline and found the cyclic AMP content to be increased by 40%. These workers employed a threshold relaxant concentration for taenia of 2 .5 x 10~8m adrenaline, but guinea-pig bronchial muscle is more sensitive to adrenaline and will relax with 5x 10~10m [Blument h a l and Brody, 1969], The relaxant concentrations of adrenaline in bronchial muscle arc thus of a similar order of magnitude as anti anaphylactic concentrations and it is conceivable that in both cases a rapid new formation of cyclic AMP may take place.…”

Section: Inhibition Of the Anaphylactic Mechanism By Sympathomimetic mentioning

confidence: 99%

Inhibition of the Anaphylactic Mechanism by Sympathomimetic Amines

Assem

Schild²

1971

Int Arch Allergy Immunol

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“…In asthmatic patients, glucagon presents a relaxant action on the airway smooth muscle inducing an improvement in the lung function [62,63], however this effect of glucagon needs to be further elucidated since some studies did not show any significant bronchodilator effect of glucagon on these patients [64,65]. Despite this controversy about the bronchodilator effect of glucagon in asthmatics, the lungs of rats express glucagon receptor (GcgR), and glucagon relaxes guinea pig bronchiolar smooth muscle in vitro independently of β-adrenergic receptor stimulation [66,67]. We showed that glucagon inhibited the allergenevoked histamine release from rat subcutaneous tissue fragments in vitro (Figure 1 (Figure 1).…”

Section: Hyperglycemic Hormones and Asthmamentioning

confidence: 99%

The Yin Yang of Hormones that Control Glucose Homeostasis in Asthma

Insuela¹,

Silva²,

Martins³

et al. 2013

J Allergy Ther

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Asthma is a chronic inflammatory disease whose prevalence has increased in the last 50 years. Several hormones can determine the course of asthma pathogenesis. Furthermore, some endocrine disorders, including diabetes and obesity, have been identified as important factors that influence the prevalence of asthma. These endocrine disorders are characterized by presenting an imbalance in blood hormones levels that regulate glucose metabolism, including hyperglycemic and hypoglycemic hormones. This review gives an update of the state-of-the-art concerning the effect of hormones that control glucose homeostasis on asthma pathogenesis and development. Here, we proposed that while hypoglycemic hormones, including insulin and leptin aggravate asthma, the hyperglycemic hormones, as glucagon, glucocorticoids and epinephrine, have a protective effect on asthma.

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Studies on the mechanism of drug-induced bronchiolar relaxation in the guinea pig

Cited by 16 publications

References 8 publications

Glucagon induces airway smooth muscle relaxation by nitric oxide and prostaglandin E2

Glucagon induces airway smooth muscle relaxation by nitric oxide and prostaglandin E2

Inhibition of the Anaphylactic Mechanism by Sympathomimetic Amines

The Yin Yang of Hormones that Control Glucose Homeostasis in Asthma

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