Differential effects of UTP, ATP, and adenosine on ciliary activity of human nasal epithelial cells

1 Cystic Fibrosis/Pulmonary Research and Treatment Center, 2 Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599-7248 The purinergic regulation of ciliary activity was studied using small, continuously superfused explants of human nasal epithelium. The P2Y 2 purinoceptor (P2Y 2 -R) was identified as the major purinoceptor regulating ciliary beat frequency (CBF); UTP (EC 50 = 4.7 µM), ATP, and adenosine-5'- O- (3-thiotriphosphate) elicited similar maximal responses, approximately twofold over baseline. ATP, however, elicited a post-peak sustained plateau in CBF (1.83 ± 0.1-fold), whereas the post-peak CBF response to UTP declined over 15 min to a low-level plateau (1.36 ± 0.16-fold). UDP also stimulated ciliary beating, probably via P2Y 6 -R, with a maximal effect approximately one-half that elicited by P2Y 2 -R stimulation. Not indicated were P2Y 1 -R-, P2Y 4 -R-, or P2Y 11 -R-mediated effects. A 2B -receptor agonists elicited sustained responses in CBF approximately equal to those from UTP/ATP [5'-( N -ethylcarboxamido)adenosine, EC 50 = 0.09 µM; adenosine, EC 50 = 0.7 µM]. Surprisingly, ADP elicited a sustained stimulation in CBF. The ADP effect and the post-peak sustained portion of the ATP response in CBF were inhibited by the A 2 -R antagonist 8-( p -sulfophenyl)theophylline. Hence, ATP affects ciliary activity through P2Y 2 -R and, after an apparent ectohydrolysis to adenosine, through A 2B AR. cilia; ciliated cells; purinergic agonists; regulation