5-Hydroxytryptamine Receptors, Especially the 5-HT4 Receptor, in Guinea Pig Urinary Bladder

Yoshida, Akira; Yamashita, Yasuko; Kaibara, Muneshige; Taniyama, Kohtaro; Tanaka, Nobuyuki

doi:10.1254/jjp.89.349

Cited by 12 publications

(13 citation statements)

References 20 publications

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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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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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“…In the isolated guinea pig bladder, it has been reported that 5-HT 2A and 5-HT 4 receptors are involved in enhancing purinergic transmission and that the 5-HT 3 receptor is involved in enhancing cholinergic transmission (Messori et al, 1995). Yoshida et al (2002) studied the 5-HT receptors in guinea pig urinary bladder preparations by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine release. Specific binding sites were detected evenly throughout the urinary bladder.…”

Section: Peripheral Targetsmentioning

confidence: 99%

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Andersson

Wein²

2004

Pharmacol Rev

452

364

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“…Several in vitro studies have shown that the contractile effect of mammalian detrusor in response to 5-HT exposure is mediated by activation of 5-HT 2 , 5-HT 3 , and 5-HT 4 receptors (Yoshida et al, 2002). In the human detrusor, 5-HT potentiates the neurogenic contractions by activating the 5-HT 4 receptor type .…”

mentioning

confidence: 99%

Characterization of Prejunctional Serotonin Receptors Modulating [³H]Acetylcholine Release in the Human Detrusor

D׳Agostino¹,

Condino²,

Gallinari³

et al. 2005

J Pharmacol Exp Ther

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Bladder overactivity (OAB) is a chronic and debilitating lower urinary tract (LUT) disorder that affects millions of individuals worldwide. LUT symptoms associated with OAB, such as urgency and urinary incontinence, cause a hygienic and social concern to patients, but their current pharmacological treatment is largely inadequate due to the lack of uroselectivity. Although OAB etiology remains multifactorial and poorly understood, increasing evidence indicates that serotonin [5-hydroxytryptamine (5-HT)] is an endogenous substance involved in the control of micturition at central and peripheral sites. In this study, we demonstrated the presence of three distinct 5-HT receptors localized at parasympathetic nerve terminals of the human bladder by measuring electrically evoked tritiated acetylcholine release in isolated detrusor strips. These prejunctional receptors, involved in both positive and negative feedback mechanisms regulating cholinergic transmission, have been characterized by means of three highly selective 5-HT antagonists for 5-HT 4 , 5-HT 7 , and 5-HT 1A receptors,. Under these conditions, we confirmed the facilitatory role of 5-HT 4 heteroreceptors on acetylcholine release and revealed for the first time the occurrence of 5-HT 7 and 5-HT 1A heteroreceptors with a facilitatory and an inhibitory action, respectively. Our findings strengthen the novel concept for the use of recently patented selective 5-HT agonists and antagonists for the control of OAB dysfunctions associated with inflammatory conditions, although their therapeutic efficacy needs to be explored in the clinical setting.

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5-Hydroxytryptamine Receptors, Especially the 5-HT4 Receptor, in Guinea Pig Urinary Bladder

Cited by 12 publications

References 20 publications

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Characterization of Prejunctional Serotonin Receptors Modulating [³H]Acetylcholine Release in the Human Detrusor

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5-Hydroxytryptamine Receptors, Especially the 5-HT4 Receptor, in Guinea Pig Urinary Bladder

Cited by 12 publications

References 20 publications

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Characterization of Prejunctional Serotonin Receptors Modulating [3H]Acetylcholine Release in the Human Detrusor

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Characterization of Prejunctional Serotonin Receptors Modulating [³H]Acetylcholine Release in the Human Detrusor