Rabbit conjunctival epithelium transports fluid, and P2Y2(2) receptor agonists stimulate Cl- and fluid secretion

Rabbit conjunctival epithelium exhibits UTP-dependent Cl- secretion into th e tears. We investigated whether fluid secretion also takes place. Short-ci rcuit current (I-sc) was 14.9 +/- 1.4 alphaA/cm(2) (n = 16). Four P2Y(2) pu rinergic receptor agonists [UTP and the novel compounds INS365, INS306, and INS440 (Inspire Pharmaceuticals)] added apically (10 muM) resulted in temp orary (similar to 30 min) I-sc increases (88%, 66%, 57%, and 28%, respectiv ely; n = 4 each). Importantly, the conjunctiva transported fluid from seros a to mucosa at a rate of 6.5 +/- 0.7 mul.h(-1).cm(-2) (range 2.1-15.3, n = 20). Fluid transport was stimulated by mucosal additions of 10 muM: 1) UTP, from 7.4 +/- 2.3 to 10.7 +/- 3.3 mul.h(-1).cm(-2), n = 5; and 2) INS365, f rom 6.3 +/- 1.0 to 9.8 +/- 2.5 mul.h(-1).cm(-2), n = 5. Fluid transport was abolished by 1 mM ouabain (n 5 5) and was drastically inhibited by 300 muM quinidine (from 6.4 +/- 1.2 to 3.6 +/- 1.0 mul.h(-1).cm(-2), n = 4). We co nclude that this epithelium secretes fluid actively and that P2Y(2) agonist s stimulate both Cl- and fluid secretions.