4.7 μM) (20). UDP, the principal agonist for P2Y6, increased the chloride secretion to 44% of the UTP response, which is similar magnitude in magnitude in terms of ciliary beat frequency (20). This finding indicates that the P2Y6 receptor is likely to be active. Besides, we have eliminated the possibility of UTP contamina- tion from UDP preparation by addition of hexokinase and glu- cose. This point was not clearly noted in the previous reports concerning P2Y6 characterization in the airway epithelium (20). Another P1 purinergic agonist, adenosine, also activated chlo- ride secretion, which was inhibited by a non-specific adenosine receptor blocker, 8-SPT (21). We examined further how much P2X receptors are function- ally implicated in nasal polyp using αβmeATP and BzATP. The αβATP is an agonist for P2X1 and P2X3, and BzATP is for P2X1, P2X2, and P2X7 (22). P2X receptors could not be detect- ed pharmacologically, which indicates that P2X receptors do not have a significant role compared to P2Y receptors. This is contrary to the report which described these agonists having large responses in lung-derived cultured cells (23). The CFTR activator, genistein (24), did not induce a CFTR current, which may be attributed to an altered localization of CFTR in the nasal polyp (25). If NO, generated by the application of NO substrate (L-arginine) or NO donor (SNP), has a regulatory effect on the CFTR or ENaC, it can serve as a medical, therapeutic strategy for nasal polyps. However, there was no beneficial effect at high concentrations of L-arginine and SNP, both in the absence and presence of amiloride in nasal polyps, which is similar to the observation in cultured human nasal epithelium (26). In conclusion, the multiple P2Y receptors were functioning at the apical membrane of the nasal polyp in situ. However, P2X agonists, the CFTR activator, and NO-producing drugs did not have a beneficial effect on nasal polyps in situ. REFERENCES 1. Wynn R, Har-El G. Recurrence rates after endoscopic sinus surgery for massive sinus polyposis. Laryngoscope. 2004 May;114(5):811-3. 2. Bernstein JM, Yankaskas JR. Increased ion transport in cultured nasal polyp epithelial cells. Arch Otolaryngol Head Neck Surg. 1994 Sep; 120(9):993-6. 3. Boeynaems JM, Communi D, Gonzalez NS, Robaye B. Overview of the P2 receptors. Semin Thromb Hemost. 2005 Apr;31(2):139-49. 4. Lazarowski ER, Tarran R, Grubb BR, van Heusden CA, Okada S, Boucher RC. Nucleotide release provides a mechanism for airway sur- face liquid homeostasis. J Biol Chem. 2004 Aug 27;279(35):36855-64. 5. Stoos BA, Garcia NH, Garvin JL. Nitric oxide inhibits sodium reab- sorption in the isolated perfused cortical collecting duct. J Am Soc Nephrol. 1995 Jul;6(1):89-94. 6. Compeau CG, Rotstein OD, Tohda H, Marunaka Y, Rafii B, Slutsky AS, et al. Endotoxin-stimulated alveolar macrophages impair lung epithelial Na+ transport by an L-Arg-dependent mechanism. Am J Physiol. 1994 May;266(5 Pt 1):C1330-41. 7. Dong YJ, Chao AC, Kouyama K, Hsu YP, Bocian RC, Moss RB, et al. Activation of CFTR chloride current by nitric oxide in human T Lee JH et al.: Ion Channel Modulators in Nasal Polyps 79 lymphocytes. EMBO J. 1995 Jun 15;14(12):2700-7. 8. Ramis I, Lorente J, Rosello′-Catafau J, Quesada P, Gelpi′E, Bulbena O. Differential activity of nitric oxide synthase in human nasal mucosa and polyps. Eur Respir J. 1996 Feb;9(2):202-6. 9. Kang BH, Huang NC, Wang HW. Possible involvement of nitric oxide and peroxynitrite in nasal polyposis. Am J Rhinol. 2004 Jul-Aug;18(4): 191-6. 10. Jaffe LF, Nuccitelli R. An ultrasensitive vibrating probe for measuring steady extracellular currents. J Cell Biol. 1974 Nov;63(2 Pt 1):614-28. 11. Nicholas RA, Watt WC, Lazarowski ER, Li Q, Harden K. Uridine nucleotide selectivity of three phospholipase C-activating P2 recep- tors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor. Mol Pharmacol. 1996 Aug;50(2):224-9. 12. Al-Nakkash L, Hu S, Li M, Hwang TC. A common mechanism for cystic fibrosis transmembrane conductance regulator protein activa- tion by genistein and benzimidazolone analogs. J Pharmacol Exp Ther. 2001 Feb;296(2):464-72. 13. Boucher RC, Stutts MJ, Knowles MR, Cantley L, Gatzy JT. Na+ trans- port in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. J Clin Invest. 1986 Nov;78(5): 1245-52. 14. Knowles MR, Stutts MJ, Spock A, Fischer N, Gatzy JT, Boucher RC. Abnormal ion permeation through cystic fibrosis respiratory epitheli- um. Science. 1983 Sep 9;221(4615):1067-70. 15. Stutts MJ, Fitz JG, Paradiso AM, Boucher RC. Multiple modes of reg- ulation of airway epithelial chloride secretion by extracellular ATP. Am J Physiol. 1994 Nov;267(5 Pt 1):C1442-51. 16. McCarty NA, McDonough S, Cohen BN, Riordan JR, Davidson N, Lester HA. Voltage-dependent block of the cystic fibrosis transmem- brane conductance regulator Cl- channel by two closely related ary- laminobenzoates. J Gen Physiol. 1993 Jul;102(1):1-23. 17. Nicholas RA, Lazarowski ER, Watt WC, Li Q, Boyer J, Harden TK. Pharmacological and second messenger signalling selectivities of cloned P2Y receptors. J Auton Pharmacol. 1996 Dec;16(6):319-23. 18. Kennedy C, Qi AD, Herold CL, Harden TK, Nicholas RA. ATP, an agonist at the rat P2Y(4) receptor, is an antagonist at the human P2Y(4) receptor. Mol Pharmacol. 2000 May;57(5):926-31. 19. Paradiso AM, Ribeiro CM, Boucher RC. Polarized signaling via puri- noceptors in normal and cystic fibrosis airway epithelia. J Gen Physiol. 2001 Jan;117(1):53-67. 20. Morse DM, Smullen JL, Davis CW. Differential effects of UTP, ATP, and adenosine on ciliary activity of human nasal epithelial cells. Am J Physiol Cell Physiol. 2001 Jun;280(6):C1485-97. 21. Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Phar- macol Rev. 1998 Sep;50(3):413-92. 22. Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Se′gue′la P, et al. International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev. 2001 Mar;53(1):107-18. 23. Taylor AL, Schwiebert LM, Smith JJ, King C, Jones JR, Sorscher EJ, Schwiebert EM. Epithelial P2X purinergic receptor channel expres- sion and function. J Clin Invest. 1999 Oct;104(7):875-84. 24. Al-Nakkash L, Hu S, Li M, Hwang TC. A common mechanism for cystic fibrosis transmembrane conductance regulator protein activa- tion by genistein and benzimidazolone analogs. J Pharmacol Exp Ther. 2001 Feb;296(2):464-72. 25. Jang YJ, Lee CH. Localization of cystic fibrosis transmembrane con- ductance regulator in epithelial cells of nasal polyps and postoperative polypoid mucosae. Acta Otolaryngol. 2001 Jan;121(1):93-7. 26. Hess A, Bloch W, Rocker J, Peters S, Stennert E, Addicks K, et al. Detection of nitric oxide synthases in physiological and pathophysio- logical processes of the nasal mucosa. HNO. 2000 Jul;48(7):489-95.