Inhaled ATP causes mucin release from goblet cells of intact rats

Secretion of mucins from airway epithelial cells has been studied almost ex clusively using in vitro cell culture systems. Our understanding of in vivo secretion is greatly limited due to the unavailable of both suitable model systems and adequate assays. It has been reported that A TTP induces mucin release from the cultured primary tracheal surface epithelial cell, but th ere is no clear demonstration of the effect of ATP on mucin release in vivo , which is important to understand the mechanism of mucin release in vivo a nd also to devise means for regulation of mucin release. The objective of t his experiment was to see if inhaled AIP could stimulate airway mucin relea se in intact rats using both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. The results were: (I) a new monoclonal antibody (mAbR T03) developed against purified rat mucins specifically recognized high-mol ecular-mass mucins; (2) ELISA results with conventional gel-filtration assa y results are virtually superimposable; (3) inhalation of A IP in intact ra ts resulted in a dose-independent increase in the amount of mucins in the t racheal lavage fluid with a concomitant decrease in the number of mucin-pos itive cells in the trachea. We conclude that extracellular ATP can stimulat e mucin release from the airway in vivo, and the present rat inhalation sys tem combined with ELISA of the airway secretions should serve a useful mode l for studying the pharmacology of airway mucin secretion in vivo.