scholarly journals Role of the serotonergic system in urethral continence reflexes during sneezing in rats

2018 ◽  
Vol 315 (1) ◽  
pp. F79-F85 ◽  
Author(s):  
Takahisa Suzuki ◽  
Takahiro Shimizu ◽  
Joonbeom Kwon ◽  
Eiichiro Takaoka ◽  
Satoru Yoshikawa ◽  
...  
Keyword(s):  
Female Rats ◽  
Normal Female ◽  
Urethral Pressure ◽  
Leak Point Pressure ◽  
Synthesis Inhibitor ◽  
Female Adult ◽  
Adult Rats ◽  
Urethral Closure ◽  
Point Pressure

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.

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

2009 ◽  
Vol 297 (4) ◽  
pp. F1024-F1031 ◽  
Author(s):  
Minoru Miyazato ◽  
Yasuhiro Kaiho ◽  
Izumi Kamo ◽  
Takeya Kitta ◽  
Michael B. Chancellor ◽  
...  
Keyword(s):  
Receptor Subtypes ◽  
Normal Female ◽  
Urethral Pressure ◽  
Female Adult ◽  
Adult Rats ◽  
Way 100635 ◽  
Urethral Closure ◽  
Point Pressure ◽  
It Application

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-HT1A agonist), mCPP (a 5-HT2B/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-HT1A antagonist, and RS-102221 (it), a selective 5-HT2C 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-HT2C receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT1A inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT2C receptors and inhibitory 5-HT receptors other than the 5-HT1A subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT2C could be effective for the treatment of SUI.

Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats

2007 ◽  
Vol 292 (2) ◽  
pp. F639-F646 ◽  
Author(s):  
Yasuhiro Kaiho ◽  
Izumi Kamo ◽  
Michael B. Chancellor ◽  
Yoichi Arai ◽  
William C. de Groat ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Normal Female ◽  
Urethral Pressure ◽  
Adult Rats ◽  
Urethral Orifice ◽  
Norepinephrine Reuptake Inhibitor ◽  
Point Pressure ◽  
Selective Blocker ◽  
Norepinephrine Reuptake

To clarify the role of noradrenergic pathways in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of the norepinephrine reuptake inhibitor nisoxetine and α-adrenoceptor antagonists phentolamine (nonspecific blocker) and prazosin (α1-receptor-selective blocker) on the neurally evoked urethral continence reflex induced by sneezing in rats. The amplitude 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, intrathecal (it) phentolamine (0.02 nmol) and prazosin (0.02 nmol) decreased A-URS by 11.9 and 15.7%, respectively, without affecting UBP. In both normal and VD rats, intravenous (iv) application of nisoxetine (1 mg/kg) increased A-URS by 17.2 and 18.3% and UBP by 23.7 and 32.7%, respectively. Phentolamine or prazosin (both it) eliminated nisoxetine-induced increases in A-URS, but not the increases in UBP, which were, however, suppressed by iv phentolamine (5 mg/kg) or prazosin (1 mg/kg). Sneezing induced fluid leakage from the urethral orifice in VD rats, but not in normal rats. In VD rats, S-LPP was increased by 30.2% by iv nisoxetine. Application of phentolamine and prazosin (both it) decreased S-LPP by 15.7 and 20.6%, respectively, and nisoxetine induced increases in S-LPP to 13.2 and 12.3%, respectively. These results indicate that activation of the noradrenergic system by a norepinephrine reuptake inhibitor can prevent SUI via α1-adrenoceptors by enhancing the sneeze-induced active urethral closure mechanism at the spinal level and augmenting UBP at the periphery.

scholarly journals Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats

2008 ◽  
Vol 295 (1) ◽  
pp. F264-F271 ◽  
Author(s):  
Minoru Miyazato ◽  
Yasuhiro Kaiho ◽  
Izumi Kamo ◽  
Michael B. Chancellor ◽  
Kimio Sugaya ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Control Level ◽  
Female Rats ◽  
Urethral Pressure ◽  
Adrenoceptor Antagonist ◽  
Closure Mechanism ◽  
Urethral Orifice ◽  
Point Pressure ◽  
Vaginal Distension

We investigated the effect of duloxetine, a norepinephrine (NE) and serotonin (5-HT) reuptake inhibitor, on the neurally evoked urethral continence reflex induced by sneezing in rats. To clarify the role of noradrenergic and serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we examined the effect of duloxetine followed by intrathecal (it) methiothepin maleate (5-HT receptor and α1-adrenoceptor antagonist) or terazosin or idazoxan (selective α1- and α2-adrenoceptor antagonists, respectively). Amplitude 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 adult female rats and rats with SUI induced by vaginal distension (VD). In normal and VD rats, intravenous application of duloxetine (1 mg/kg) increased A-URS by 35% and 34% and UBP by 21% and 34%, respectively. Sneezing-induced fluid leakage from the urethral orifice was observed in VD rats but not in normal rats. S-LPP was increased from 39.1 to 92.2 cmH2O by intravenous duloxetine in incontinent VD rats. Duloxetine-mediated enhancement of A-URS was inhibited by terazosin but not methiothepin maleate (it). In addition, simultaneous intrathecal application of methiothepin and terazosin induced a reduction in A-URS during sneezing, which was not increased by intravenous duloxetine. However, the reduced A-URS after intrathecal application of methiothepin and terazosin returned to the control level when duloxetine (iv) was applied after intrathecal idazoxan administration. These results indicate that duloxetine can prevent SUI by facilitating noradrenergic and serotonergic systems in the spinal cord to enhance the sneeze-induced active urethral closure mechanism.

scholarly journals Effect of GABA-T on Reproductive Function in Female Rats

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 567
Author(s):  
Wenyu Si ◽  
Hailing Li ◽  
Tiezhu Kang ◽  
Jing Ye ◽  
Zhiqiu Yao ◽  
...  
Keyword(s):  
Mrna Level ◽  
Reproductive Function ◽  
Female Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Lactation Performance ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Expression Of Genes

This study explored the role of γ-aminobutyric acid transaminase (GABA-T) in the puberty and reproductive performance of female rats. Immunofluorescence technique, quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution of GABA-T and the expression of genes and hormones in female rats, respectively. The results showed that GABA-T was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and periventricular nucleus (PeN) of the hypothalamus, and in the adenohypophysis, ovarian granulosa cells and oocytes. Abat mRNA level at 28 d was lowest in the hypothalamus and the pituitary; at puberty, it was lowest in the ovary. Abat mRNA level was highest in adults in the hypothalamus; at infancy and puberty, it was highest in the pituitary; and at 21 d it was highest in the ovary. After vigabatrin (GABA-T irreversible inhibitor) was added to hypothalamus cells, the levels of Abat mRNA and Rfrp-3 mRNA were significantly reduced, but Gnrh mRNA increased at the dose of 25 and 50 μg/mL; Kiss1 mRNA was significantly increased but Gabbr1 mRNA was reduced at the 50 μg/mL dose. In prepubertal rats injected with vigabatrin, puberty onset was delayed. Abat mRNA, Kiss1 mRNA and Gnrh mRNA levels were significantly reduced, but Rfrp-3 mRNA level increased in the hypothalamus. Vigabatrin reduced the concentrations of GABA-T, luteinizing hormone (LH) and progesterone (P4), and the ovarian index. Lactation performance was reduced in adult rats with vigabatrin treatment. Four hours after vigabatrin injection, the concentrations of GABA-T and LH were significantly reduced in adult and 25 d rats, but follicle-stimulating hormone (FSH) increased in 25 d rats. In conclusion, GABA-T affects the reproductive function of female rats by regulating the levels of Gnrh, Kiss1 and Rfrp-3 in the hypothalamus as well as the concentrations of LH and P4.

COMPARISON OF ??1-ADRENOCEPTOR AGONISTS IN CANINE URETHRAL PRESSURE PROFILOMETRY AND ABDOMINAL LEAK POINT PRESSURE MODELS

2001 ◽  
pp. 1555-1559 ◽  
Author(s):  
MICHAEL E. BRUNE ◽  
ALYSSA B. O???NEILL ◽  
DONNA M. GAUVIN ◽  
SWETA P. KATWALA ◽  
ROBERT J. ALTENBACH ◽  
...  
Keyword(s):  
Urethral Pressure ◽  
Leak Point Pressure ◽  
Point Pressure ◽  
Adrenoceptor Agonists

scholarly journals Rat Mesenchymal Stem Cell Secretome Promotes Elastogenesis and Facilitates Recovery from Simulated Childbirth Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1395-1406 ◽  
Author(s):  
Charuspong Dissaranan ◽  
Michelle A. Cruz ◽  
Matthew J. Kiedrowski ◽  
Brian M. Balog ◽  
Bradley C. Gill ◽  
...  
Keyword(s):  
Female Rats ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Paracrine Factors ◽  
Pelvic Organs ◽  
Point Pressure ◽  
Urethral Smooth Muscle ◽  
And Function ◽  
Vaginal Distension

Vaginal delivery is a risk factor for stress urinary incontinence (SUI). Mesenchymal stem cells (MSCs) home to injured organs and can facilitate repair. The goal of this study was to determine if MSCs home to pelvic organs after simulated childbirth injury and facilitate recovery from SUI via paracrine factors. Three experiments were performed. Eighteen female rats received vaginal distension (VD) or sham VD and labeled intravenous (IV) MSCs to investigate if MSCs home to the pelvic organs. Whole-organ imaging and immunofluorescence were performed 1 week later. Thirty-four female rats received VD and IV MSCs, VD and IV saline, or sham VD and IV saline to investigate if MSCs accelerate recovery of continence. Twenty-nine female rats received VD and periurethral concentrated conditioned media (CCM), VD and periurethral control media, or sham VD and periurethral control media to investigate if factors secreted by MSCs accelerate recovery from VD. Urethral histology and function were assessed 1 week later. Significantly more MSCs were observed in the urethra, vagina, and spleen after VD compared to sham VD. Continence as measured by leak point pressure (LPP) was significantly reduced after VD in rats treated with saline or control media compared to sham VD but not in those given MSCs or CCM. External urethral sphincter (EUS) function as measured by electromyography (EMG) was not improved with MSCs or CCM. Rats treated with MSCs or CCM demonstrated an increase in elastin fibers near the EUS and urethral smooth muscle more similar to that of sham-injured animals than rats treated with saline or control media. MSCs homed to the urethra and vagina and facilitated recovery of continence most likely via secretion of paracrine factors. Both MSCs and CCM have promise as novel noninvasive therapies for SUI.

COMPARISON OF α1-ADRENOCEPTOR AGONISTS IN CANINE URETHRAL PRESSURE PROFILOMETRY AND ABDOMINAL LEAK POINT PRESSURE MODELS

2001 ◽  
Vol 166 (4) ◽  
pp. 1555-1559 ◽  
Author(s):  
MICHAEL E. BRUNE ◽  
ALYSSA B. O’NEILL ◽  
DONNA M. GAUVIN ◽  
SWETA P. KATWALA ◽  
ROBERT J. ALTENBACH ◽  
...  
Keyword(s):  
Urethral Pressure ◽  
Leak Point Pressure ◽  
Point Pressure ◽  
Adrenoceptor Agonists
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