Acute Effects of Serotonin on Rat Bladder Contractility

Kim, Hyung Jee; Lee, Gilho; Kim, Dong Hee; Lee, Suk Jae; Yoon, Dae Wui; Cho, Jae Heung

doi:10.1159/000048416

Cited by 12 publications

(10 citation statements)

References 15 publications

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“…pBOO, bladder wall thickness tended to increase (15), and similar alterations might occur, at least in part, in this rat model. In the present study, 5-HT induced bladder contraction, as described in reports on rats, cats, dogs, and humans (6,(10)(11)(12)26). The contractile responses to 5-HT was significantly enhanced by pBOO, and expression of mRNA encoding the 5-HT 2A and 5-HT 2B receptors was increased in the detrusor muscle layer following pBOO.…”

Section: Discussionsupporting

confidence: 83%

Increased expression of 5-HT2A and 5-HT2B receptors in detrusor muscle after partial bladder outlet obstruction in rats

et al. 2015

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Serotonin (5-hydroxytryptamine; 5-HT)-induced bladder contraction is enhanced after partial bladder outlet obstruction (pBOO) in rats. We investigated time-dependent changes in bladder contraction and expression of 5-HT 2A and 5-HT 2B receptor mRNA in bladder tissue to elucidate the mechanism of this enhancement. On day 3 and 7 after pBOO, contractile responses of isolated rat bladder strips to 5-HT were increased compared with that in sham-operated rats; on day 14, the response had decreased to the same level as that in sham rat bladders. In contrast, carbacholinduced contraction was not enhanced by pBOO at any time point. In sham rats, 5-HT 2A receptor mRNA was expressed in the urothelium, and 5-HT 2B receptor mRNA was expressed in the detrusor muscle layer. In pBOO rats, both receptor mRNAs were increased in the detrusor muscle and subserosal layers, but not in the urothelium. The increase of 5-HT 2A receptor mRNA was maintained from day 3 to day 14 after pBOO, and 5-HT 2B receptor mRNA was increased on day 7 after pBOO. These results suggested that pBOO induced up-regulation of the 5-HT 2A and 5-HT 2B receptors in the detrusor muscle and subserosal layers of the bladder, and such up-regulation may be related to the enhanced bladder contractile response to 5-HT.Partial bladder outlet obstruction (pBOO) secondary to benign prostate hyperplasia has been considered an important factor associated with lower urinary tract symptoms (LUTS). LUTS include voiding symptoms (e.g., weak urine stream and urinary retention) and storage symptoms (e.g., urinary frequency, urgency and nocturia) (1). Voiding symptom is attributed to increased urethral resistance due to static and dynamic prostatic obstruction. In contrast, the mechanism responsible for storage symptoms secondary to pBOO remains unknown. To clarify the mechanism, several changes in the bladder have been investigated with animal models of pBOO (13,14,17). In these animal models, urothelium, subserosal layer, and detrusor muscle layer of the bladder are thickened (2, 7, 24). These morphological alterations result in some functional changes, such as detrusor overactivity. These morphological and functional alterations reach different states at different time points after pBOO (2,16,19). Therefore, both morphological and functional changes must be evaluated at several time points to reveal the mechanisms responsible for the storage symptoms secondary to pBOO. One of the important functional changes in the bladder with pBOO is the contractile response associated with detrusor overactivity. Contractile responses to ATP and acetylcholine are changed by pBOO; however, descriptions of these changes are not consistent among reports (2,7,19,25). Therefore, the myogenic change caused by pBOO is not fully understood. Serotonin (5-hydroxytryptamine; 5-HT) is a mono-

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Section: Discussionsupporting

confidence: 83%

Increased expression of 5-HT2A and 5-HT2B receptors in detrusor muscle after partial bladder outlet obstruction in rats

et al. 2015

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“…*P < 0.05 compared to controls (chi-square test). (19) tested the in vitro acute effects of serotonin on rat bladder contractility, specifically investigating the effects of serotonin on the rat detrusor and determined the drugs that could inhibit the serotonin-induced detrusor contractions. The results showed that the 5-HT2 antagonist blocked the effect of serotonininduced contractions and that the 5-HT2 receptor was mainly responsible for serotonin-induced contractions of the rat detrusor.…”

Section: Discussionmentioning

confidence: 99%

Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence?

Schwanke

Bittencourt

Noronha

et al. 2007

Braz J Med Biol Res

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The regulation of bladder function is influenced by central serotonergic modulation. Several genetic polymorphisms related to serotonin control have been described in the literature. T102C polymorphism of the serotonin receptor 2A gene (5-HT2A) has been shown to be associated with certain diseases such as non-fatal acute myocardial infarction, essential hypertension, and alcoholism. In the present study, we examined the association between 5-HT2A gene polymorphism and urinary incontinence in the elderly. A case-control study was performed in 298 elderly community dwellers enrolled in the Gravataí-GENESIS Project, Brazil, which studies gene-environmental interactions in aging and age-related diseases. Clinical, physical, biochemical, and molecular analyses were performed on volunteers. 5-HT2A genotyping was determined by PCR-RFLP techniques using the HpaII restriction enzyme. The subjects had a mean age of 68.05 ± 6.35 years (60-100 years), with 16.9% males and 83.1% females. The C allele frequency was 0.494 and the T allele frequency was 0.506. The CC genotype frequency was 21.78%, the CT genotype frequency was 55.24% and the TT genotype frequency was 22.98%. We found an independent significant association between the TT genotype (35.7%) and urinary incontinence (OR = 2.06, 95%CI = 1.16-3.65). Additionally, urinary incontinence was associated with functional dependence and systolic hypertension. The results suggest a possible genetic influence on urinary incontinence involving the serotonergic pathway. Further investigations including urodynamic evaluation will be performed to better explain our findings.

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“…In the bladder, contractile responses to serotonin are mediated by the 5-HT 2 receptor [Kim et al, 2002;Yoshida et al, 2002]. Interestingly, the 5-HT 2A receptor has been shown to concentrate in caveolae of circular and longitudinal smooth muscle of rat intestine [Fiorica-Howells et al, 2002] and to associate with caveolin-1 in glioma cells [Bhatnagar et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

Cristofaro

Peters

Yalla

et al. 2006

Neurourology and Urodynamics

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Aims: Caveolae are cholesterol-rich plasmalemmal microdomains that serve as sites for sequestration of signaling proteins and thus may facilitate, organize, and integrate responses to extracellular stimuli. While previous studies in the bladder have demonstrated alterations in caveolae with particular physiologic or pathologic conditions, little attention has been focused on the functional signi¢cance of these organelles. Therefore, the purpose of this study was to investigate the role of caveolae in the modulation of receptor-mediated signal transduction and determine the presence and localization of caveolin proteins in bladder tissue. Methods: Contractile responses to physiologic agonists were measured in rat bladder tissue before and after disruption of caveolae achieved by depleting membrane cholesterol with methyl-b-cyclodextrin. Stimulation with agonists was repeated after caveolae were restored as a result of cholesterol replenishment. RT-PCR, immmunohistochemistry, and Western blotting were used to determine the expression and localization of caveolin mRNA and proteins. Results: Following caveolae disruption, contractile responses to angiotensin II and serotonin were attenuated, whereas responses to bradykinin and phenylephrine were augmented. Cholesterol replenishment restored responses towards baseline. Carbachol and KCl induced contractions were not a¡ected by caveolae disruption. Ultrastructure analysis con¢rmed loss of caveolae following cholesterol depletion with cyclodextrin and caveolae restoration following cholesterol replacement. Gene and protein expression of caveolin-1, -2, and -3 was detected in bladder tissue. Immunoreactivity for all three caveolins was observed in smooth muscle cells throughout the bladder. Conclusions: The functional e¡ects of cholesterol depletion on speci¢c agonist-induced contractile events and the expression of all three caveolins in bladder smooth muscle support a central role for caveolae in regulation of selective G-protein-coupled receptor signaling pathways in bladder smooth muscle. Thus, caveolae serve to di¡erentially regulate bladder smooth muscle by a stimulus-dependent potentiation or inhibition of bladder contraction.

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Acute Effects of Serotonin on Rat Bladder Contractility

Cited by 12 publications

References 15 publications

<b>Increased expression of 5-HT</b><b><sub>2A</sub></b><b> and 5-HT</b><b><sub>2B</sub></b><b> receptors in detrusor muscle after partial bladder outlet obstruction in </b><b>rats </b>

<b>Increased expression of 5-HT</b><b><sub>2A</sub></b><b> and 5-HT</b><b><sub>2B</sub></b><b> receptors in detrusor muscle after partial bladder outlet obstruction in </b><b>rats </b>

Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence?

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

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