Role of prostaglandin I₂ in the bronchoconstriction-triggered cough response in guinea pigs

Abstract

Purpose/Aim of the study: Methacholine chloride (MCh) inhalation causes bronchoconstriction and cough. Following MCh-induced bronchoconstriction, metabolic products of prostaglandin I₂ (PGI₂) increase in bronchoalveolar lavage fluid (BALF), suggesting that PGI₂ plays a role in the cough response. Accordingly, we used an experimental guinea pig model to evaluate the role of PGI₂ in the bronchoconstriction-triggered cough response. Materials and Methods: Experiment 1: The concentration of PGF_1α, a stable metabolite of PGI₂, in BALF was assessed in animals exposed to nebulized MCh and animals exposed to nebulized saline. Experiment 2: Bronchoconstriction and cough were assessed in 3 groups of animals after MCh inhalation (a saline group, low-dose PGI₂ group, and high-dose PGI₂ group). Enhanced pause (Penh) was used as a measure of bronchoconstriction. Experiment 3: Bronchoconstriction and cough were assessed in 3 groups of animals (groups administered saline, a low dose of a specific antagonist of the PGI₂ receptor (IP antagonist), and a high dose of a specific IP antagonist). Results: The PGF_1α concentration in BALF was significantly higher in the bronchoconstriction group than in the control group. In animals administered high-dose PGI₂, the MCh-induced increase in Penh was significantly suppressed, and the number of coughs induced by bronchoconstriction was significantly decreased. In animals treated with a high dose of an IP antagonist, the MCh-induced increase in Penh was not affected, and the number of coughs increased. Conclusions: Our results suggest that PGI₂ ameliorates a bronchoconstriction-triggered cough. The measurement and administration of PGI₂ may assist in the diagnosis and treatment, respectively, of the cough response triggered by bronchoconstriction.

Keywords:

• Prostaglandin I₂
• Prostaglandin I₂ receptor
• cough response to bronchoconstriction
• cough-variant asthma
• guinea pig
• Penh

Acknowledgments

We wish to thank Ms. Miki Kashiwano for her assistance with the experiments. We would like to thank Editage (www.editage.jp) for English language editing.

Declaration of interest

The authors report no conflict of interest associated with the manuscript.

Additional information

Funding

We had received a PGI₂ analog from Astellas Pharma Inc.This work was supported by a grant from Novartis Pharma Research Grants 2016.