Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva.
The purpose of the present study was to understand the mechanisms of action of diquafosol, a stable derivative of uridine 5'-triphosphate, on Cl(-) transport across the isolated rabbit conjunctiva. Rabbit conjunctivas were isolated and mounted in a modified Ussing chamber. Under short-circuit conditions, the effects were determined of mucosal (tear) side diquafosol application on the short-circuit current (Isc). Diquafosol rapidly and dose-dependently increased the Isc at concentrations ranging from 0.1 to 968 microM when added to the mucosal side of the conjunctiva. In the absence of the serosal Cl(-), the Isc induced by 10 microM diquafosol was substantially reduced. On the contrary, in the absence of mucosal side Na(+), the diquafosol-induced increases in Isc were unchanged. Following 45-min preincubation, the P2Y(2) antagonist suramin inhibited the diquafosol-induced increases in the Isc whereas the P2Y(1) antagonist pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid had no effect. These studies suggest that diquafosol stimulates net Cl(-) secretion from the serosal to the mucosal side via stimulation of P2Y(2) receptors in the rabbit conjunctiva.
Murakami
Tadahiro
T
Research and Development Center, Santen Pharmaceutical Co., Ltd., Ikoma, Japan. tadahiro.murakami@santen.co.jp
Fujihara
Tsutomu
T
Horibe
Yoshihide
Y
Nakamura
Masatsugu
M
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003228:Conjunctiva / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011122:Polyphosphates / Q000494:pharmacology*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D012964:Sodium / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014500:Uracil Nucleotides / Q000494:pharmacology*
D002712:Chlorides; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D014500:Uracil Nucleotides; D013498:Suramin; C403315:diquafosol; D012964:Sodium