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

Am J Physiol Renal Physiol. 2012 Jan 15;302(2):F251-63. doi: 10.1152/ajprenal.00378.2011. Epub 2011 Oct 12.

Abstract

In many species, β3-adrenergic receptors (β3-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 β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-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. β3-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 μM), 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 μM), a β3-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 μM) did not affect the DSM cell resting membrane potential and K(+) conductance. Although β3-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 β3-ARs species differences.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Ethanolamines / pharmacology
  • Female
  • Guinea Pigs
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Receptors, Adrenergic, beta-3 / metabolism*
  • Sulfonamides / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Ethanolamines
  • L 755507
  • Receptors, Adrenergic, beta-3
  • Sulfonamides
  • BRL 37344