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Study on Physiological Roles of Stimulation of Prostaglandin E2 Receptor Subtype EP2 in Urethral Function in Rats.
Kurihara, Ryoko; Ishizu, Kenichiro; Takamatsu, Hajime; Yoshino, Taiji; Masuda, Noriyuki.
Afiliación
  • Kurihara R; Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
  • Ishizu K; Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
  • Takamatsu H; Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
  • Yoshino T; Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
  • Masuda N; Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
Low Urin Tract Symptoms ; 8(2): 125-9, 2016 May.
Article en En | MEDLINE | ID: mdl-27111625
OBJECTIVES: We investigated the relaxant effect of stimulation of prostaglandin E2 (PGE2 ) 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 PGE2 and selective EP2 receptor agonist CP-533,536. METHODS: Effects of PGE2 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 PGE2 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 PGE2 and CP-533,536 (0.003-0.3 mg/kg intravenously) on urethral perfusion pressure (UPP) in anesthetized rats were also evaluated. RESULTS: PGE2 concentration-dependently increased the accumulation of cAMP in cells expressing rat EP2 (EC50 value = 1.3 nmol/L) and EP4 receptors (EC50 value = 17 nmol/L). While CP-533,536 similarly increased the accumulation of cAMP in cells expressing rat EP2 receptors (EC50 value = 3.0 nmol/L), no such effects were noted in cells expressing rat EP4 receptors up to 10 µmol/L. Both PGE2 and CP-533,536 produced relaxation and increased cAMP levels in urethral tissues in a concentration-dependent manner. PGE2 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Uretra / Subtipo EP2 de Receptores de Prostaglandina E Límite: Animals Idioma: En Revista: Low Urin Tract Symptoms Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Australia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Uretra / Subtipo EP2 de Receptores de Prostaglandina E Límite: Animals Idioma: En Revista: Low Urin Tract Symptoms Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Australia