TY - JOUR T1 - Nucleotide Stimulation of Cl<sup>−</sup> Secretion in the Pigmented Rabbit Conjunctiva JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 53 LP - 59 VL - 291 IS - 1 AU - Ken-Ichi Hosoya AU - Hideo Ueda AU - Kwang-Jin Kim AU - Vincent H. L. Lee Y1 - 1999/10/01 UR - http://jpet.aspetjournals.org/content/291/1/53.abstract N2 - We evaluated the role of extracellular UTP and other nucleotides in the regulation of active ion transport across the pigmented rabbit conjunctiva. When added to the mucosal side of the conjunctiva, UTP (0.01–1000 μM), increased the short-circuit current by up to 14.6 ± 2.1 μA/cm2. The half-maximal concentration was 11.4 ± 2.3 μM. The serosal absence of Cl−, serosal presence of 10 μM bumetanide, and mucosal presence of 0.3 mMN-phenylanthranilic acid significantly reduced the change in the short-circuit current (ΔIsc) induced by 10 μM UTP by 78, 77, and 42%, respectively. Mucosal 10 μM UTP significantly increased 36Cl flux in the serosal-to-mucosal direction by 0.17 μEq/cm2/h, while not affecting mucosal-to-serosal36Cl flux. By contrast, 22Na transport in either direction was unaffected. The rank order of ΔIsc elicited by adenosine and nucleotides was consistent with the predominant involvement of P2Y purinergic receptors in the UTP effect on conjunctival ion transport. Moreover, the ΔIsc elicited by UTP was inhibited by 0.05 and 1 mM suramin (a P2-purinergic receptor antagonist), resulting in a rightward shift of the half-maximal concentration to 106.7 ± 1.3 μM. In conclusion, the primary effect of UTP on ion transport in the pigmented rabbit conjunctiva is stimulation of Cl− secretion, possibly at the P2Y2 and/or the P2Y4 receptor on the mucosal side of the tissue. Because of the coupling of fluid flow with Cl− secretion, UTP or its analogs may be considered for stimulating transconjunctival fluid flow in the dry-eye state. The American Society for Pharmacology and Experimental Therapeutics ER -