Activation of ??1D Adrenergic Receptors in the Rat Urothelium Facilitates the Micturition Reflex

Ishihama, Hiroko; Momota, Yoshiharu; Yanase, Haruko; Wang, Xiaojun; Groat, William C. de; Kawatani, Masahito

doi:10.1097/00005392-200601000-00121

Cited by 44 publications

(78 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, neither intravenous administration of tamsulosin (0.4 μg/kg) nor intravesical infusion of tamsulosin (20 μM) or silodosin (0.2 μM) significantly affected ICI during continuous infusion cystometrograms, while in our previous study intravenous administration of naftpidil (1.0 mg/kg) significantly prolonged ICI. One explanation for this ent nerve activity induced by bladder distention and prolonged ICI during continuous infusion cystometrograms (14). The present results taken together with our previous data indicated that activation of both α 1A and α 1D receptors in the urothelium might affect the afferent pathway and increase voiding frequency.…”

Section: The Effect Of Tamsulosin On Na-induced Ici Reductionsupporting

confidence: 77%

“…In rat urothelium, mRNAs for all three subtypes of α 1 adrenergic receptors were detected. Previously we showed that α 1D receptors facilitate the mechanosensitive bladder afferent nerve activity partly through distention-induced ATP release from the urothelium (14). In the present study, we used subtype selective α 1 antagonists, tamsulosin (α 1A /α 1D ) and silodosin (α 1A superselective) to investigate the involvement of urothelial α 1A receptors in modulating the micturition reflex.…”

mentioning

confidence: 90%

“…How urothelial α 1A acts on the afferent pathway remains unknown. Regarding the α 1D receptor, we previously demonstrated that intravenous administration of naftopidil inhibited the release of ATP into the bladder lumen induced by bladder distention, suggesting that urothelial α 1D receptors enhance afferent nerve activity through increasing ATP release from urothelial cells during the storage phase (14). In the present study, neither intravenous administration of tamsulosin (0.4 μg/kg) nor intravesical infusion of tamsulosin (20 μM) or silodosin (0.2 μM) significantly affected ICI during continuous infusion cystometrograms, while in our previous study intravenous administration of naftpidil (1.0 mg/kg) significantly prolonged ICI.…”

Section: The Effect Of Tamsulosin On Na-induced Ici Reductionmentioning

confidence: 99%

See 2 more Smart Citations

The involvement of urothelial α1A adrenergic receptor in controlling the micturition reflex

et al. 2008

Self Cite

View full text Add to dashboard Cite

The current study was undertaken in an attempt to characterize the functional properties of urothelial α 1A adrenergic receptors, especially in modulating the micturition reflex. The expression of α 1A receptors in rat bladder was analyzed by immunohistochemistry and Western blotting. As a functional study, we obtained continuous infusion cystometrograms in conscious rats using noradrenaline (NA) and subtype selective α 1 adrenergic receptor antagonists, tamsulosin (α 1A /α 1D selective) and silodosin (α 1A superselective). α 1A receptors were immunohistochemically detected in rat urothelium. Intravesical infusion of NA (60 μM) significantly shortened the intercontraction interval (ICI). Pretreatment with tamsulosin at a dose of 0.4 μg/kg i.v. abolished intravesical NA infusioninduced reduction of ICI. Neither intravesical infusion of tamsulosin (20 μM) nor that of silodosin (0.2 μM) significantly altered ICI. After intravesical infusion of silodosin, intravesical NA infusion did not affect ICI. Urothelial α 1A receptors might modulate bladder afferent activity under pathophysiological conditions with augmented concentrations of NA in blood or urine. α 1 adrenergic receptor antagonists have been the predominant form of medical therapy for the treatment of lower urinary tract symptoms in benign prostatic hyperplasia (BPH) (17). α 1 blockers were initially designed to improve voiding symptoms in BPH such as hesitancy and slow urinary flow, since α 1A adrenergic receptors enhance prostatic and urethral smooth muscle contraction to increase the resistance of urinary outflow. It turned out later that this therapy is also effective for storage symptoms such as frequency and urgency (8), suggesting the existence of another target mechanism of these drugs different from releasing bladder outlet obstruction (18). α 1 adrenergic receptors have been found at various sites in the nervous system controlling the bladder function. Intrathecal injection of α 1 antagonist increased the bladder capacity and decreased the vesical pressure during bladder contraction in rats (15, 16). In the parasympathetic ganglia of cats, α 1 antagonist prazosin inhibited the hypogastric nerveinduced facilitation of cholinergic transmission (19). In addition to their presence in the nervous system, all three subtypes of α 1 adrenergic receptors (α 1A , α 1B and α 1D ) have been identified in human and rat bladder (13,21,24). The functions of the three different subtypes in nerves and the urinary bladder were not studied until recently due to a lack of specific antagonists for each receptor subtype. The urothelium has been appreciated to be a potential modulator of bladder sensory systems because of its neuron-like properties capable of detecting mechanical or chemical stimuli and releasing a number of signaling molecules (7). The urothelial cells express diverse sensor molecules including transient receptor potential (TRP) channels (5, 6), amiloride/mechanosensitive Na + channels (ENaC) (12), receptors for purines (20,25) and acetylcho-

show abstract

Section: The Effect Of Tamsulosin On Na-induced Ici Reductionsupporting

confidence: 77%

mentioning

confidence: 90%

Section: The Effect Of Tamsulosin On Na-induced Ici Reductionmentioning

confidence: 99%

See 1 more Smart Citation

The involvement of urothelial α1A adrenergic receptor in controlling the micturition reflex

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…70 The α 1D adrenergic receptor is expressed within the bladder urothelium, and it seems that tonic activation of urothelial α 1D receptors by catecholamines might be involved in bladder sensory mechanisms. 71 Catecholamines could be released from nerves adjacent to the urothelium or from nerves that innervate nearby blood vessels, as the suburothelial region receives a rich blood supply. It has been shown that stimulation of both α-adrenergic and β-adrenergic receptors on urothelial cells evokes the release of NO.…”

Section: Role Of Adrenergic Receptors In Bladder Outlet Obstructionmentioning

confidence: 99%

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

2007

View full text Add to dashboard Cite

SUMMARYAlthough the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.

show abstract

“…Thus, it remains to be established where the α 1 -adrenoceptors mediating LUTS relief in men are located. Of note, a possible location in the bladder does not necessarily imply those on detrusor smooth muscle cells but may equally involve those in lower urinary tract blood vessels (30), the urothelium, and/or afferent nerves (31), possibilities which have been tested experimentally to a limited extent only.…”

Section: Efficacymentioning

confidence: 99%

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: α-Blockers in the Treatment of Male Voiding Dysfunction — How Do They Work and Why Do They Differ in Tolerability?

Michel

2010

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. α 1 -Adrenoceptor antagonists are the mainstay of medical treatment of male voiding dysfunction which typically is attributed to benign prostatic hyperplasia. While original concepts have assumed that they relieve voiding dysfunction by relaxing prostatic smooth muscle, newer data indicate that their therapeutic effects at least partly occur independent of prostatic relaxation, perhaps involving direct effects on blood vessels, urothelium, afferent nerves, and/or smooth muscle of the urinary bladder. The adverse event profiles differ among α 1 -adrenoceptor antagonists, with tamsulosin having a particularly good cardiovascular tolerability. While this was originally attributed to its selectivity for α 1A -adrenoceptors, it appears that alfuzosin which lacks subtype-selectivity, has a very similar tolerability. In contrast, doxazosin and terazosin, which are chemically and pharmacologically more closely related to alfuzosin than to tamsulosin, appear to have more side effects attributable to the cardiovascular system. More recent data indicate that tolerability differences between α 1 -adrenoceptor antagonists may at least partly relate to pharmacokinetic rather than to pharmacodynamic differences. Taken together, these data emphasize the idea that concepts about drug efficacy and tolerability despite being highly plausible may not necessarily be true and always require thorough experimental testing.

show abstract

Activation of ??1D Adrenergic Receptors in the Rat Urothelium Facilitates the Micturition Reflex

Cited by 44 publications

References 11 publications

The involvement of urothelial α1A adrenergic receptor in controlling the micturition reflex

The involvement of urothelial α1A adrenergic receptor in controlling the micturition reflex

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: α-Blockers in the Treatment of Male Voiding Dysfunction — How Do They Work and Why Do They Differ in Tolerability?

Contact Info

Product

Resources

About