Clinical and Experimental Otorhinolaryngology Vol. 1, No. 2: 75-79, June 2008 DOI 10.3342/ceo.2008.1.2.75 Original Article Modulators of Ion Transport in Nasal Polyps: An in situ Measurement of Short-Circuit Current Jun Ho Lee, MD, PhD Chae-Seo Rhee, MD, PhD Dae Woo Kim, MD Chul Hee Lee, MD, PhD Department of Otorhinolaryngology, College of Medicine and Research Center for Sensory Organs, Medical Research Center, Seoul National University, Seoul, Korea Objectives. To examine possible modulators of the ion transport through the apical membrane of the nasal polyps. Methods. The study was conducted using the freshly-excised nasal polyps from the patients with chronic sinusitis. A volt- age-sensitive vibrating probe technique was introduced to monitor the short-circuit current across the apical mem- brane of the polyp at 37℃. Results. In the presence of amiloride, Adenosine 5’-triphosphate induced 4,4’-Diisothiocyanatostilbene-2,2’-disulfonic acid- sensitive chloride current. Uridine 5’-diphosphate was less potent than Uridine 5’-triphosphate, and adenosine increased chloride secretion, which was blocked by the antagonist, 8-(p-sulfophenyl) theophylline on adenosine receptor. Based on the pharmacologic profiles, multiple purinergic receptors, including P2Y2, P2Y6, and P1 receptors, were functionally expressed. However, P2X receptor agonists ( , -methyleneadenosine 5’-triphosphate and 2’- & 3’-O-[4-benzoyl-ben- zoyl] adenosine 5’-triphosphate), Cystic fibrosis conductance regulator (CFTR) activator (genistein), nitric oxide substrate (L-arginine), and nitric oxide donor (sodium nitroprusside) had no significant effect on the short circuit current. Conclusion. Among tested drugs, P2Y receptor agonists were major modulators of ion transport in nasal polyps in situ. Key Words. Nasal polyps, CFTR, Purinergic receptors, Genistein, Nitric oxide, Vibrating Probe INTRODUCTION Nasal polyps are a prevalent medical condition, affecting 1-4% of the population. Controversies persist regarding the manage- ment of nasal polyps because the exact etiology remains unclear. Corticosteroids are beneficial in reducing the size of polyps and preventing recurrences, but proper control of nasal polyposis is a challenging task in clinical situations. It has been reported that the recurrence rate is as high as 60% in patients with severe nasal polyposis (1). Nasal polyps are characterized by stromal edema and increased inflammatory cells. Hyperabsorption of Na+ and increased Cl- permeability may account for stromal edema formation (2). Received April 1, 2008 Accepted after revision April 29, 2008 Corresponding author : Chul Hee Lee, MD Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul National Univeristy Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea Tel : +82-2-2072-3646, Fax : +82-2-745-2387 E-mail : chulhee@snu.ac.kr This study was supported by Clinical Research Institute at Seoul National University Hospital (Grant # 03-2004-011-0). 75 There are two main families of purinergic receptors (adeno- sine and P2 receptors). The P2 receptors can in turn be divided into two families (ligand-gated P2X and the G protein-coupled P2Y receptors). To date, seven P2X receptors (P2X1-7) and eight P2Y receptors (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11-14) have been cloned and characterized, and are accepted as valid members in mammals (3). The activation of chloride secretion via purinergic receptors has been reported in the ciliated respiratory epithelial cells cultured from nasal polyps (4). On the other hand, there are reports that the nitric oxide (NO) inhibits Na+ absorption in rat cortical collecting ducts (5) and rat distal lung epithelium (6), while NO activates the cystic fibrosis transmembrane conduc- tance regulator (CFTR) current in human T lymphocytes (7). The total amount of NO is higher in polyps than normal mucosa (8), and inducible nitric oxide synthase (iNOS) is highly expressed in nasal polyps (9). The aim of the present study was to exam- ine the effects of ion transport modulators, including purinergic agonists, NO donors, and the CFTR chloride channel activator on nasal polyps in situ using a voltage-sensitive vibrating probe technique.