Modulators of Ion Transport in Nasal Polyps: An in situ Measurement of Short-Circuit Current

ABSTRACT

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 voltage-sensitive vibrating probe technique was introduced to monitor the short-circuit current across the apical membrane of the polyp at 37degrees C. RESULTS: In the presence of amiloride, Adenosine 5'-triphosphate induced 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acidsensitive 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 P2Y(2), P2Y(6), and P1 receptors, were functionally expressed. However, P2X receptor agonists (alpha,beta-methyleneadenosine 5'-triphosphate and 2'- & 3'-O-[4-benzoyl-benzoyl] 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.