Involvement of β3-adrenoceptors in the inhibitory control of cholinergic activity in human bladder: Direct evidence by [3H]-acetylcholine release experiments in the isolated detrusor

D׳Agostino, Gianluigi; Condino, Anna Maria; Calvi, Paolo M.

doi:10.1016/j.ejphar.2015.03.074

Cited by 52 publications

(63 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This release may be inhibited by β 3 -AR agonist stimulation, but it seems unlikely that the massive release of ACh that occurs in the detrusor during voiding can be prevented by the inhibitory action of β 3 -AR agonists on cholinergic nerve endings. This is in accordance with studies showing that the capacity of β 3 -AR agonists to inhibit electrically induced ACh release is only partial [22,23], and with the finding that β 3 -AR agonists have little or no effect on the voiding contraction in humans.…”

Section: β-Ar Agonists: Mechanism Of Actionsupporting

confidence: 92%

“…Since there is evidence that there is a release of ACh during bladder filling [41,42], the finding that activation of prejunctional β 3 -ARs can decrease ACh release resulting in an inhibitory control of parasympathetic activity may be of interest [22,23]. Electrical stimulation of nerves in the bladder releases ACh from the bladder cholinergic nerves, thus mimicking parasympathetic outflow from the spinal cord.…”

Section: β-Ar Agonists: Mechanism Of Actionmentioning

confidence: 99%

See 1 more Smart Citation

On the Site and Mechanism of Action of β3-Adrenoceptor Agonists in the Bladder

Andersson

2017

Int Neurourol J

View full text Add to dashboard Cite

The clinical success of mirabegron as the first β3-adrenoceptor (AR) agonist for treatment of the overactive bladder (OAB) syndrome, has resulted in substantial interest in its site and mechanism of action. Even if the adrenergic innervation of the bladder and urethra has been well studied, the location(s) of β3-ARs in different structures within the bladder wall and urethra, and the mode(s) of action of β3-AR stimulation have still not been established. The recent demonstration of β3-ARs on cholinergic nerve terminals with no immunoreactivity in urothelium or detrusor smooth muscle, is not in agreement with previous morphological studies, and functional data strongly suggest that β3-ARs can be found these structures. However, recent studies suggest that the β3-ARs on detrusor smooth muscle may not be the functionally most relevant. The assumption that β3-AR activation during bladder filling inhibits acetylcholine release from parasympathetic neurons by a prejunctional mechanism and that this decreases bladder micromotions that generate afferent activity, is an attractive hypothesis. It does not exclude that other mechanisms may be contributing, and supports combined approaches to reduce afferent activity for treatment of the OAB syndrome.

show abstract

Section: β-Ar Agonists: Mechanism Of Actionsupporting

confidence: 92%

Section: β-Ar Agonists: Mechanism Of Actionmentioning

confidence: 99%

On the Site and Mechanism of Action of β3-Adrenoceptor Agonists in the Bladder

Andersson

2017

Int Neurourol J

View full text Add to dashboard Cite

show abstract

“…Our study did not find differences between genotypes and anticholinergic medication failure. As mentioned previously, the β‐3 receptor is implicated in inhibition of cholinergic nerve signals in vitro and more recently this was suggested by work in vivo . Gurocak and colleagues studied 34 children with lower urinary tract symptoms.…”

Section: Discussionmentioning

confidence: 87%

Role of β‐3 adrenergic receptor polymorphism in overactive bladder

Meekins

Murphy

Grenier

et al. 2019

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims Women with overactive bladder (OAB) have a higher frequency of a single‐nucleotide polymorphism (SNP) at codon 64 of the β‐3 adrenergic receptor gene (ADRB3). Since the SNP results in an amino acid substitution that could theoretically alter receptor protein function, we hypothesized that those with the SNP would display greater OAB symptom severity. Therefore we aimed to compare OAB severity between women with this SNP and women with the wild type genotype. Methods A retrospective cohort study was performed in women with bothersome OAB from two academic institutions. Banked blood samples were tested for the codon 64 SNP. Women were divided into two groups based on genotype: wild‐type (WT) and heterozygous (HZ). We compared mean OAB Symptom Severity questionnaire (OAB‐q) scores between groups using t tests. Linear regression was performed to control for potential confounders. Results Of the 303 women with OAB, 254 (83.8%) had the WT genotype, and 49 (16.2%) the HZ genotype. There were no homozygous women for the rare allele. The majority were Caucasian (86%) and non‐Hispanic (97%). There were no significant differences in mean OAB‐q symptom severity scores (WT 21.2 ± 7 vs HZ 22.0 ± 6.6; P = 0.49) and quality of life scores (WT 39.6 ± 15.5 vs HZ 39.1 ± 16.6; P = 0.83) between groups. These remained nonsignificant in a linear regression model. Conclusions In a predominantly non‐Hispanic, Caucasian population of women with bothersome OAB, symptom severity was not related to ADRB3 codon 64 SNP genotype.

show abstract

“…Inhibition of neuronal acetylcholine release by presynaptic β3-adrenoceptors has been reported in human and rat bladders, 30,31 which may modulate spontaneous contractions and afferent activities of the bladder. However, in some species, including human, sympathetic nerve fibres predominantly innervate the blood vessels, and there is only a sparse adrenergic innervation of the detrusor.…”

Section: Introductionmentioning

confidence: 99%