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

Nucleotide Stimulation of Clminus 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 (Delta 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 Delta 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 Delta 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.

0022-3565/99/2911-0053$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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