Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

Afeli SA, Hristov KL, Petkov GV. Do beta 3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?. Am J Physiol Renal Physiol 302: F251-F263, 2012. First published October 12, 2011; doi:10.1152/ajprenal.00378.2011.-In many species, beta 3-adrenergic receptors (beta 3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether beta 3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective beta 3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. beta 3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 mu M), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 mu M), a beta 3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 mu M) did not affect the DSM cell resting membrane potential and K+ conductance. Although beta 3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM beta 3-ARs species differences.