Selective P2Y2 receptor agonists stimulate vaginal moisture in ovariectomized rabbits.
OBJECTIVE
To determine the expression of P2Y(2) receptors in vaginal and cervical tissues and the effects of P2Y(2) receptor agonists INS45973 and INS365 on vaginal moisture.


METHODS
Pilot in vivo and histological study using animal subjects.


METHODS
Experimental laboratory research.


METHODS
Female New Zealand White rabbits were used for in vivo studies and female cynomolgus monkey (Macaca fascicularis) was used for in situ hybridization.


METHODS
Rabbits were kept intact or ovariectomized. Two weeks after ovariectomy, animals received daily vaginal instillation of vehicle or drugs for 16 days.


METHODS
Vaginal moisture was assessed in rabbits on 4 separate days during the treatment period. The P2Y(2) receptor mRNA distribution was assessed by in situ hybridization of monkey vagina and cervix.


RESULTS
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 P2Y(2) receptor mRNA was localized to endocervical and cervical gland, epithelium, and stratified squamous epithelium of the vagina.


CONCLUSIONS
INS45973 and INS365 may interact with P2Y(2) receptors in the cervix and vagina to stimulate vaginal moisture in the estrogen (E)-deprived state. The P2Y(2) receptor agonists provide a potential nonhormonal alternative for treating vaginal dryness in postmenopausal women.
Min
Kweonsik
K
Department of Urology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Munarriz
Ricardo
R
Yerxa
Benjamin R
BR
Goldstein
Irwin
I
Shaver
Sammy R
SR
Cowlen
Matthew S
MS
Traish
Abdulmaged M
AM
D000818:Animals; D005260:Female; D017403:In Situ Hybridization; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D010052:Ovariectomy; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058473:Receptors, Purinergic P2Y2; D014500:Uracil Nucleotides; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*
D009883:Ophthalmic Solutions; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D014500:Uracil Nucleotides; C403315:diquafosol