Am J Physiol Cell Physiol Journal of Neurophysiology
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Am J Physiol Cell Physiol 281: C595-C602, 2001;
0363-6143/01 $5.00
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Vol. 281, Issue 2, C595-C602, August 2001

Rabbit conjunctival epithelium transports fluid, and P2Y22 receptor agonists stimulate Clminus and fluid secretion

Yansui Li1, Kunyan Kuang1, Benjamin Yerxa2, Quan Wen1, Heinz Rosskothen1, and Jorge Fischbarg1,3

Departments of 1 Ophthalmology and 3 Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032; and 2 Inspire Pharmaceuticals, Incorporated, Durham, North Carolina 27703

Rabbit conjunctival epithelium exhibits UTP-dependent Cl- secretion into the tears. We investigated whether fluid secretion also takes place. Short-circuit current (Isc) was 14.9 ± 1.4 µA/cm2 (n = 16). Four P2Y2 purinergic receptor agonists [UTP and the novel compounds INS365, INS306, and INS440 (Inspire Pharmaceuticals)] added apically (10 µM) resulted in temporary (~30 min) Isc increases (88%, 66%, 57%, and 28%, respectively; n = 4 each). Importantly, the conjunctiva transported fluid from serosa to mucosa at a rate of 6.5 ± 0.7 µl · h-1 · cm-2 (range 2.1-15.3, n = 20). Fluid transport was stimulated by mucosal additions of 10 µM: 1) UTP, from 7.4 ± 2.3 to 10.7 ± 3.3 µl · h-1 · cm-2, n = 5; and 2) INS365, from 6.3 ± 1.0 to 9.8 ± 2.5 µl · h-1 · cm-2, n = 5. Fluid transport was abolished by 1 mM ouabain (n = 5) and was drastically inhibited by 300 µM quinidine (from 6.4 ± 1.2 to 3.6 ± 1.0 µl · h-1 · cm-2, n = 4). We conclude that this epithelium secretes fluid actively and that P2Y2 agonists stimulate both Cl- and fluid secretions.

dry eye; purinergic; adenosine 5'-triphosphate; uridine 5'-triphosphate; INS365; short-circuit current


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