Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Mar;387(3):215-24.
doi: 10.1007/s00210-013-0936-2. Epub 2013 Nov 10.

Do β-adrenoceptor agonists induce homologous or heterologous desensitization in rat urinary bladder?

Martin C Michel  1
Affiliations

Do β-adrenoceptor agonists induce homologous or heterologous desensitization in rat urinary bladder?

Martin C Michel. Naunyn Schmiedebergs Arch Pharmacol. 2014 Mar.

Abstract

β3-Adrenoceptor agonists have recently been introduced for the symptomatic treatment of the overactive bladder syndrome. As such treatment is not curative, long-term treatment is anticipated to be required. As the susceptibility of β3-adrenoceptors to undergo agonist-induced desensitization is cell type- and tissue-dependent, we have explored whether pre-treatment with a β-adrenoceptor agonist will attenuate subsequent relaxation responses to freshly added agonist using rat urinary bladder as a model. We have used the prototypical β-adrenoceptor agonist isoprenaline, the β2-selective fenoterol and the β3-selective CL 316,243 and mirabegron as well as the receptor-independent bladder relaxant forskolin. We show that a 6-h pre-treatment with agonist can significantly reduce subsequent relaxation against KCl-induced smooth muscle tone, but agonist-induced desensitization was also observed with longer pre-treatments or against passive tension. The agonist-induced desensitization was prominent for the β2 component of rat bladder relaxation but much weaker or even absent for the β3 component. Moreover, β-adrenoceptor agonist pre-treatment reduced contractile responses to the muscarinic agonist carbachol and the receptor-independent stimulus KCl. Taken together these data do not support the hypothesis that the long-term clinical efficacy of β3-adrenoceptor agonists in the treatment of the overactive bladder syndrome will be limited by receptor desensitization. Rather they raise the possibility that such treatment may not only cause smooth muscle relaxation but also may attenuate hyper-contractility of the bladder.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Pharmacol Exp Ther. 1994 Dec;271(3):1253-8 - PubMed
    1. Endocrinology. 1996 Jun;137(6):2638-41 - PubMed
    1. Neurourol Urodyn. 2007;26(6):752-6 - PubMed
    1. Eur Urol. 2005 Aug;48(2):303-8 - PubMed
    1. Naunyn Schmiedebergs Arch Pharmacol. 2013 Mar;386(3):247-53 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources