Research article summary (published 27 Jul 2009):

Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats.

Full Abstract

To clarify the role of spinal serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of intrathecal (it) application of 8-OH-DPAT (a 5-HT(1A) agonist), mCPP (a 5-HT(2B/2C) agonist), and fluoxetine (a serotonin reuptake inhibitor) using a rat model that can examine the neurally evoked continence reflex during sneezing. Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, 8-OH-DPAT decreased A-URS by 48.9%, whereas mCPP increased A-URS by 33.6%. However, A-URS was not changed after fluoxetine. 8-OH-DPAT, mCPP, or fluoxetine did not alter UBP. The effect of 8-OH-DPAT and mCPP was antagonized by WAY-100635 (it), a selective 5-HT(1A) antagonist, and RS-102221 (it), a selective 5-HT(2C) antagonist, respectively. Fluoxetine in the presence of WAY-100635 did not change either A-URS or UBP, but fluoxetine in the presence of RS-102221 decreased A-URS. In VD rats, S-LPP was decreased by 14.6 cmH2O after 8-OH-DPAT, whereas it was increased by 12.8 cmH2O after mCPP. However, S-LPP was not changed after fluoxetine. These results indicate that activation of 5-HT(2C) receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT(1A) inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT(2C) receptors and inhibitory 5-HT receptors other than the 5-HT(1A) subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT(2C) could be effective for the treatment of SUI.

Author information

Author/s: Miyazato, Minoru (M); Kaiho, Yasuhiro (Y); Kamo, Izumi (I); Kitta, Takeya (T); Chancellor, Michael B (MB); Sugaya, Kimio (K); Arai, Yoichi (Y); de Groat, William C (WC); Yoshimura, Naoki (N);

Affiliation: Dept. of Urology, Univ. of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Grants: AR-049398 (Agency:NIAMS NIH HHS) ; DK-055387 (Agency:NIDDK NIH HHS) ; DK-067226 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol), published in United States. (Language: eng)

Reference: 2009-Oct; vol 297 (issue 4) : pp F1024-31

Dates: Created 2009/09/29; Completed 2009/10/27;

PMID: 19640898, status: MEDLINE (last retrieval date: 10/27/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

8-Hydroxy-2-(di-n-propylamino)tetralin Animals Female Fluoxetine Piperazines Pressure Pyridines Rats

Rats, Sprague-Dawley Receptor, Serotonin, 5-HT1A - agonists; antagonists & inhibitors; metabolism Receptors, Serotonin, 5-HT2 - agonists; antagonists & inhibitors; metabolism Sneezing Spiro Compounds Sulfonamides Urethra - physiology Urinary Incontinence, Stress - metabolism; physiopathology

Associated Chemicals: Piperazines (0) ; Pyridines (0) ; RS 102221 (0) ; Receptors, Serotonin, 5-HT2 (0) ; Spiro Compounds (0) ; Sulfonamides (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; WAY 100635 (146714-97-8) ; Fluoxetine (54910-89-3) ; 1-(3-chlorophenyl)piperazine (6640-24-0) ; 8-Hydroxy-2-(di-n-propylamino)tetralin (78950-78-4)

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