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Study on Physiological Roles of Stimulation of Prostaglandin E 2 Receptor Subtype EP2 in Urethral Function in Rats
Author(s) -
KURIHARA Ryoko,
ISHIZU Kenichiro,
TAKAMATSU Hajime,
YOSHINO Taiji,
MASUDA Noriyuki
Publication year - 2016
Publication title -
luts: lower urinary tract symptoms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 15
eISSN - 1757-5672
pISSN - 1757-5664
DOI - 10.1111/luts.12077
Subject(s) - prostaglandin e2 receptor , receptor , endocrinology , stimulation , medicine , agonist , prostaglandin e , prostaglandin , chemistry , phenylephrine , prostaglandin e2 , biology , blood pressure
Objectives We investigated the relaxant effect of stimulation of prostaglandin E 2 ( PGE 2 ) receptor subtype EP2 as well as the involvement of a cyclic AMP ( cAMP )‐dependent pathway related to stimulation of EP2 receptors in urethral function in rats by evaluating effects of PGE 2 and selective EP2 receptor agonist CP ‐533,536. Methods Effects of PGE 2 and CP ‐533,536 on cAMP accumulation were assessed in Chinese hamster ovary ( CHO )‐ K1 cells expressing rat EP2 or EP4 receptors. Relaxant responses to PGE 2 and CP ‐533,536 (0.01–10 µmol/L) in rat urethral tissue pre‐contracted with 10 µmol/L phenylephrine were evaluated, and cAMP levels in isolated rat urethral tissue treated with these compounds were determined as well. The effects of PGE 2 and CP ‐533,536 (0.003–0.3 mg/kg intravenously) on urethral perfusion pressure ( UPP ) in anesthetized rats were also evaluated. Results PGE 2 concentration‐dependently increased the accumulation of cAMP in cells expressing rat EP2 ( EC 50 value = 1.3 nmol/L) and EP4 receptors ( EC 50 value = 17 nmol/L). While CP ‐533,536 similarly increased the accumulation of cAMP in cells expressing rat EP2 receptors ( EC 50 value = 3.0 nmol/L), no such effects were noted in cells expressing rat EP4 receptors up to 10 µmol/L. Both PGE 2 and CP ‐533,536 produced relaxation and increased cAMP levels in urethral tissues in a concentration‐dependent manner. PGE 2 and CP ‐533,536 both dose‐dependently decreased UPP in anesthetized rats. Conclusions Taken together, these results suggest that stimulation of EP2 receptors induces relaxation likely via activation of cAMP ‐dependent mechanisms in rat urethral tissue, leading to a reduction of UPP .