Role of prostaglandin E in bronchoconstriction-triggered cough response in guinea pigs.

A feature of cough variant asthma is a heightened cough response to bronchoconstriction. The mediators of this response are unknown. This study was designed to elucidate the role of lipid mediators in bronchoconstriction-triggered cough response in an experimental animal model. We examined the influence of bronchoconstriction on cell components and mediators including prostaglandin E (PGE) in bronchoalveolar lavage fluid (BALF). We studied the cough response to bronchoconstriction (CRB) by measuring the correlation between the increase in enhanced pause (Penh), an index of bronchoconstriction, and cough counts induced by methacholine (Mch) inhalation in conscious guinea pigs. We then examined the effects of intraperitoneal pretreatment with 16, 16-dimethyl-prostaglandin E (dm-PGE) on CRB and cough counts. The total number of cells and cell components in the BALF were not influenced by bronchoconstriction. While levels of PGE, prostaglandin I, and cysteinyl leukotrienes were significantly increased, levels of prostaglandin D, thromboxane B, and substance P in the BALF were not. Dm-PGE significantly decreased the Mch-induced increase in Penh. Following bronchoconstriction by additional Mch inhalation, dm-PGE produced an increase in CRB and cough counts in a dose-dependent manner. Additionally, the heightened CRB following dm-PGE treatment was suppressed by pretreatment with PGE receptor (E-prostanoid EP) -1 and EP-3 antagonists in a dose-dependent manner, but not by EP-2 and EP-4 antagonists. The EP-1 antagonist also decreased cough counts. These results suggest that PGE acts as an exacerbating factor for bronchoconstriction-triggered cough. EP1 and EP3 may provide new therapeutic targets for cough variant asthma.