Acute Effects of Uridine 5′-Triphosphate on Mucociliary Clearance in Isolated Frog Palate

Abstract

ABSTRACT

Mucociliary velocity (MCV), transepithelial potential difference (PD), cilia beat frequency (CBF), mucus collection rate, rheology, and chloride concentration [Cl⁻] were analyzed in an in vitro study using the freshly isolated frog palate exposed to an aerosol of modified Ringer's injection, followed by uridine 5′-triphosphate (UTP) 10⁻⁴ mol/L either alone or immediately preceded by aerosolization of 5 × 10⁻⁴ mol/L 4,4′-diisothiocyano-2,2′ stilbenedisulfonate (DIDS), a chloride channel blocker. UTP increased PD and decreased MCV with a positive relationship between the two. UTP promoted the appearance of copious quantities of secretion and increased the collection rate; the computed mucus depth increased by more than sixfold. There was a significant increase in both [Cl⁻] and wet weight. The increase in PD and chloride secretion led to enhanced transepithelial fluid transport and a decrease in MCV. Rheology and CBF were not affected by UTP, indicating that the main effect was on the interaction between the mucus and the cilia. All the positive effects were blockable by DIDS. The significant increase in chloride content and mucus volume and their relationship with percentage of solids indicate that UTP is an effective stimulant of mucus secretion, which is attributable to secretion of both chloride and macromolecules. The results support the presence of Ca²⁺-dependent chloride channels on the epithelial surface of the frog palate.