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

The purinergic regulation of ciliary activity was studied using small, cont inuously superfused explants of human nasal epithelium. The P2Y(2) purinoce ptor (P2Y(2)-R) was identified as the major purinoceptor regulating ciliary beat frequency (CBF); UTP (EC50 = 4.7 muM), ATP, and adenosine-5'-O-(3-thi otriphosphate) elicited similar maximal responses, approximately twofold ov er 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 cil iary beating, probably via P2Y(6)-R, with a maximal effect approximately on e-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, EC50 = 0.09 muM; adenosine, EC50 = 0.7 muM]. Surprisingly, ADP elicited a sustained stimulation in CBF. The ADP effect and the post-peak sustained portion of the ATP response in CBF were inhibit ed by the A(2)-R antagonist 8-(p-sulfophenyl) theophylline. Hence, ATP affe cts ciliary activity through P2Y(2)-R and, after an apparent ectohydrolysis to adenosine, through A(2B)AR.