Expression and functional role of β3 -adrenoceptors in the human ureter

Int J Urol. 2013 Oct;20(10):1007-14. doi: 10.1111/iju.12093. Epub 2013 Jan 29.

Abstract

Objectives: To investigate the presence of β-adrenoceptor subtypes in the human ureter, and to examine whether β(3) -adrenoceptors modulate relaxation of the human ureter.

Methods: Expression of messenger ribonucleic acid of β-adrenoceptors in the human ureter was determined by reverse transcription polymerase chain reaction, and distribution of β-adrenoceptors was examined by immunohistochemistry. In functional studies, the relaxant effects of isoproterenol, procaterol, TRK-380, salbutamol and BRL 37344 on KCl-induced contraction of the human ureter were evaluated, and the inhibitory effects of isoproterenol, procaterol and TRK-380 on electrical field stimulation-induced contractions were determined.

Results: Expression of β(1) -, β(2) - and β(3) -adrenoceptor messenger ribonucleic acid in the human ureter was confirmed by reverse transcription polymerase chain reaction. Positive staining for β(1) -, β(2) - and β(3) -adrenoceptor was identified not only in smooth muscle, but also in the urothelium of the human ureter. All β-adrenoceptor agonists decreased the tone of KCl-induced contractions of the human ureter with a rank order of relaxant effects of isoproterenol > procaterol > TRK-380 > salbutamol > BRL 37344. Furthermore, isoproterenol, procaterol and TRK-380 significantly decreased the amplitude of electrical field stimulation-induced contractions with a rank order of inhibitory effects of isoproterenol > procaterol > TRK-380.

Conclusions: Human ureteral relaxation is mediated by both β(2) - and β(3) -adrenoceptor stimulation. β(3) -Adrenoceptor agonists have the potential to relax the human ureter, and their clinical application in the treatment of ureteral stones is expected.

Keywords: TRK-380; human ureter; immunohistochemistry; reverse transcription polymerase chain reaction; β3-adrenoceptor agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Aged
  • Aged, 80 and over
  • Albuterol / pharmacology
  • Ethanolamines / pharmacology
  • Female
  • Humans
  • Isoproterenol / pharmacology
  • Male
  • Middle Aged
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / innervation
  • Muscle, Smooth / physiology*
  • Procaterol / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Adrenergic, beta-3 / genetics*
  • Receptors, Adrenergic, beta-3 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology
  • Ureter / drug effects
  • Ureter / innervation
  • Ureter / physiology*
  • Urothelium / drug effects
  • Urothelium / innervation
  • Urothelium / physiology*

Substances

  • ADRB1 protein, human
  • ADRB2 protein, human
  • ADRB3 protein, human
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Ethanolamines
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • BRL 37344
  • Isoproterenol
  • Albuterol
  • Procaterol