Vol. 291, Issue 1, 53-59, October 1999

Nucleotide Stimulation of Cl Secretion in the Pigmented Rabbit Conjunctiva¹

Ken-Ichi Hosoya² , Hideo Ueda, Kwang-Jin Kim and Vincent H. L. Lee

Departments of Pharmaceutical Sciences (K.-I.H., H.U., V.H.L.L.), Ophthalmology (V.H.L.L.), Medicine (K.-J.K.), Physiology and Biophysics (K.-J.K.), Molecular Pharmacology and Toxicology (K.-J.K.), Biomedical Engineering (K.-J.K.), and Will Rogers Institute Pulmonary Research Center (K.-J.K.), Schools of Pharmacy, Medicine, and Engineering, University of Southern California, Los Angeles, California

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 mM N-phenylanthranilic acid significantly reduced the change in the short-circuit current (Isc) 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-serosal ³⁶Cl flux. By contrast, ²²Na transport in either direction was unaffected. The rank order of Isc 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 Isc 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.