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

Abstract
The purinergic regulation of ciliary activity was studied using small, continuously superfused explants of human nasal epithelium. The P2Y2 purinoceptor (P2Y2-R) was identified as the major purinoceptor regulating ciliary beat frequency (CBF); UTP (EC50 = 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 P2Y6-R, with a maximal effect approximately one-half that elicited by P2Y2-R stimulation. Not indicated were P2Y1-R-, P2Y4-R-, or P2Y11-R-mediated effects. A2B-receptor agonists elicited sustained responses in CBF approximately equal to those from UTP/ATP [5′-( N-ethylcarboxamido)adenosine, EC50 = 0.09 μM; adenosine, EC50 = 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 A2-R antagonist 8-( p-sulfophenyl)theophylline. Hence, ATP affects ciliary activity through P2Y2-R and, after an apparent ectohydrolysis to adenosine, through A2BAR.

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