The P2Y
2 purinergic receptors are functional on
excised rabbit conjunctival surfaces, shown by the fact that the
P2Y
2 receptor agonists adenosine triphosphate
(ATP) and uridine 5′-triphosphate (UTP) induce increases in
intracellular free calcium levels, plasma membrane ionic permeability,
and chloride secretion.
13 14 15 16 17 18 19 This functional evidence is
in agreement with the detection on the ocular surface of P2Y receptor
subtype gene expression.
20 Furthermore, in airway
epithelial P2Y
2 receptor activation results in
mucin secretion from goblet cells,
21 increased bronchial
inhibitor secretion from submucosal glands,
22 surfactant
release from type II alveolar cells,
23 and increased
chloride and water transport into the airway surface
lipid.
15 17 24 25 Furthermore, in the normal rabbit,
P2Y
2 agonists stimulate tear
secretion
26 and also release glycoproteins, including
mucins from conjunctival goblet cells.
27 P2Y
2 receptor activation is considered a novel
approach in the treatment of dry eye syndrome. INS365 is a derivative
of the naturally occurring substance UTP. Similar to UTP, INS365 is a
potent and more stable selective agonist of the
P2Y
2 receptor. INS365 stimulates rabbit tear
fluid secretion, and it is being developed for treatment of dry eye
syndrome.
26