β₃ Adrenoceptor-induced cholinergic inhibition in human and rat urinary bladders involves the exchange protein directly activated by cyclic AMP 1 favoring adenosine release.

ABSTRACT:

Background and purpose

The mechanism by which β₃ receptor agonists (e.g. mirabegron) control bladder overactivity may involve adenosine release from human and rat detrusor smooth muscle. Retrograde activation of adenosine A₁ receptors reduces ACh release from cholinergic bladder nerves. β₃ -Adrenoceptors usually couple to adenylyl cyclase. Here we investigated, which of the cAMP targets, protein kinase A or the exchange protein directly activated by cAMP (EPAC) could be involved in this cholinergic inhibition of the bladder.

Experimental approach

[³ H]ACh and adenosine release from urothelium-denuded detrusor strips of cadaveric human organ donors and rats were measured by liquid scintillation spectrometry and HPLC, respectively. I

SUBMITTER: Silva I 

PROVIDER: S-EPMC7060368 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature