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, 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 microM), 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 microM; adenosine, EC(50) = 0.7 microM]. 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.
Morse
D M
DM
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA.
Smullen
J L
JL
Davis
C W
CW
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D009297:Nasal Mucosa / Q000166:cytology*; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*
D000970:Antineoplastic Agents; C546382:P2RY1 protein, human; C109734:P2RY11 protein, human; C546385:P2RY2 protein, human; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; D019830:Adenosine-5'-(N-ethylcarboxamide); C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D000242:Cyclic AMP; D000241:Adenosine; D014544:Uridine Triphosphate