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Role of the Serotonergic System in Urethral Continence Reflexes During Sneezing in Rats

Role of the Serotonergic System in Urethral Continence Reflexes During Sneezing in Rats

Takahisa Suzuki, Takahiro Shimizu, Joonbeom Kwon, Eiichiro Takaoka, Satoru Yoshikawa, Yasuhiro Sumino, Takeya Kitta, Minoru Miyazato, Hideaki Miyake, Naoki Yoshimura

Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F79-F85.

PMID: 29442547

Abstract:

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2C agonist) or LP44 (a 5-HT7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2C antagonist) and SB-269970 (a selective 5-HT7 antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2C and 5-HT7 receptors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP824958125	LP44		824958-12-5	Price

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