Beta‐3 adrenergic receptor is expressed in acetylcholine‐containing nerve fibers of the human urinary bladder: An immunohistochemical study

Abstract

We demonstrated that β3AR is abundantly located in acetylcholine-containing nerve fibers. These findings have important consequences to understand the mechanism of action of β3AR agonists currently used for the treatment of OAB.

β3‐adrenoceptor agonists inhibit carbachol‐evoked Ca2+ oscillations in murine detrusor myocytes

“…A recent study by Coelho et al. found that β3‐ARs were primarily expressed in nerve fibres in the mucosa and muscle layers of the bladder but not in urothelium or smooth muscle; however, Silva et al. showed that β3‐AR immunofluorescence was higher in the smooth muscle layer, compared with the urothelium and sub‐urothelium.…”

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

“…The body of the human bladder receives a relatively sparse innervation by noradrenergic nerves [11], and Coelho et al [12] observed that numerous smooth muscle areas were without any tyrosine-hydroxylase (key enzyme involved in noradrenaline synthesis) immunoreactive fibres. The density of noradrenergic nerves increases markedly toward the bladder neck, where the smooth muscle receives a dense noradrenergic nerve supply, particularly in the male [11].…”

“…The density of noradrenergic nerves increases markedly toward the bladder neck, where the smooth muscle receives a dense noradrenergic nerve supply, particularly in the male [11]. Noradrenergic nerves can be found also in the lamina propria of the bladder, only some of which are related to the vascular supply [11,12]. …”

“…This does not exclude the possibility that released noradrenaline exerts an inhibitory effect on bladder function by other indirect mechanisms. β 3 -ARs can be found also in other bladder structures than detrusor and urothelium [12,18]. A recent study [12] demonstrated that β 3 -ARs are abundantly located in acetylcholine (ACh)-containing nerve fibres in the the mucosa and muscular layers of the human bladder.…”

“…β 3 -ARs can be found also in other bladder structures than detrusor and urothelium [12,18]. A recent study [12] demonstrated that β 3 -ARs are abundantly located in acetylcholine (ACh)-containing nerve fibres in the the mucosa and muscular layers of the human bladder. No β 3 -AR immunoreactivity was detected on urothelial, suburothelial interstitial cells or smooth muscle cells, which is in contrast to previous findings [17,18].…”