Modulation of nerve-evoked contractions by β3-adrenoceptor agonism in human and rat isolated urinary bladder

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

“…The results of the present study are in agreement with others which have shown that β3‐AR agonists inhibit cholinergic‐mediated contractions of the detrusor induced by electric field stimulation or application of cholinergic agonists . Despite this, β3‐AR agonists have little, or no, effect on voiding contractions in humans, that are mediated by neuronal release of ACh ; therefore, at first glance it appears that the therapeutic effects of these drugs are not related to inhibition of cholinergic responses, such as those observed in the present study.…”

“…The β3‐AR agonists inhibit detrusor contractions induced by cholinergic stimulation , and much of the current debate is centred around whether these effects are brought about by a direct effect on the detrusor , inhibition of acetylcholine (ACh) release from cholinergic nerves , or a combination of both . A recent study by Silva et al.…”

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

“…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.…”

“…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.…”

What are the origins and relevance of spontaneous bladder contractions? ICI‐RS 2017

“…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.…”