Selective P2Y2 receptor agonists stimulate vaginal moisture in ovariectomized rabbits

To determine the expression of P2Y2 receptors in vaginal and cervical tissues and the effects of P2Y2 receptor agonists INS45973 and INS365 on vaginal moisture. Pilot in vivo and histological study using animal subjects. Experimental laboratory research. Female New Zealand White rabbits were used for in vivo studies and female cynomolgus monkey (Macaca fascicularis) was used for in situ hybridization. Rabbits were kept intact or ovariectomized. Two weeks after ovariectomy, animals received daily vaginal instillation of vehicle or drugs for 16 days. Vaginal moisture was assessed in rabbits on 4 separate days during the treatment period. The P2Y2 receptor mRNA distribution was assessed by in situ hybridization of monkey vagina and cervix. Compared to control, vaginal moisture was significantly diminished in ovariectomized animals treated with vehicle. INS365 (8.1%) and INS45973 (0.9%) increased vaginal moisture in ovariectomized animals to levels that were comparable to or significantly higher than control animals, respectively. In situ hybridization studies indicated that P2Y2 receptor mRNA was localized to endocervical and cervical gland, epithelium, and stratified squamous epithelium of the vagina. INS45973 and INS365 may interact with P2Y2 receptors in the cervix and vagina to stimulate vaginal moisture in the estrogen (E)-deprived state. The P2Y2 receptor agonists provide a potential nonhormonal alternative for treating vaginal dryness in postmenopausal women.