Inhibition of cholinergic neurotransmission by beta(3)-adrenoceptors depends on adenosine release and A(1)-receptor activation in human and rat urinary

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Silva, I (Author) Other; Costa, AF (Author) Other; Moreira, S (Author) Other; Ferreirinha, F (Author) Other; Magalhaes Cardoso, MT (Author) Other; Calejo, I (Author) Other; Silva Ramos, M (Author) Other; Paulo Correia de Sá (Author) ICBAS

Journal

Title: American Journal of Physiology - Renal Physiology

Vol. 313

Pages: F388-F403

ISSN: 1931-857X

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 3 Citations

Other information

Authenticus ID: P-00N-1H9

DOI: 10.1152/ajprenal.00392.2016

Abstract (EN): The direct detrusor relaxant effect of beta(3)-adrenoceptor agonists as a primary mechanism to improve overactive bladder symptoms has been questioned. Among other targets, activation of beta(3)-adrenoceptors downmodulate nerve-evoked acetylcholine (ACh) release, but there is insufficient evidence for the presence of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a retrograde messenger via prejunctional A(1) receptors to explain inhibition of cholinergic activity by beta(3)-adrenoceptors. Isoprenaline (1 mu M) decreased [H-3] ACh release from stimulated (10 Hz, 200 pulses) human (- 47 +/- 5%) and rat (- 38 +/- 1%) detrusor strips. Mirabegron (0.1 mu M, - 53 +/- 8%) and CL316,243 (1 mu M, - 37 +/- 7%) mimicked isoprenaline (1 mu M) inhibition, and their effects were prevented by blocking beta 3-adrenoceptors with L748,337 (30 nM) and SR59230A (100 nM), respectively, in human and rat detrusor. Mirabegron and isoprenaline increased extracellular adenosine in the detrusor. Blockage of A(1) receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM) or the equilibrative nucleoside transporters (ENT) with dipyridamole (0.5 mu M) prevented mirabegron and isoprenaline inhibitory effects. Dipyridamole prevented isoprenaline-induced adenosine outflow from the rat detrusor, and this effect was mimicked by the ENT1 inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI, 30 mu M). Cystometry recordings in anesthetized rats demonstrated that SR59230A, DPCPX, dipyridamole, and NBTI reversed the decrease in the voiding frequency caused by isoprenaline (0.1-1,000 nM). Data suggest that inhibition of cholinergic neurotransmission by beta(3)-adrenoceptors results from adenosine release via equilibrative nucleoside transporters and prejunctional A(1)-receptor stimulation in human and rat urinary bladder.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16