Gene expressions and mechanical functions of α1-adrenoceptor subtypes in mouse ureter

World J Urol. 2009 Dec;27(6):775-80. doi: 10.1007/s00345-009-0396-y.

Abstract

Purpose: This study was performed to characterize the α1-adrenoceptor subtypes in mouse ureters as regards gene expressions and contractile functions.

Methods: The mRNAs for these subtypes were quantified by the real-time quantitative reverse transcription polymerase chain reaction. In a functional study, α1-adrenoceptor antagonists were evaluated against the noradrenaline-induced contraction in mouse isolated ureteral preparations.

Results: In mouse ureter, the relative mRNA expression levels for α1a-, α1b- and α1d-adrenoceptors were 74.5, 14.3 and 11.2%, respectively. Adrenaline and noradrenaline each produced a concentration-dependent phasic contraction (pD 2 values, 5.73±0.05 and 5.69±0.06, respectively). Prazosin (non-selective α1-adrenoceptor antagonist), silodosin (selective α1A-adrenoceptor antagonist), and BMY-7378 (selective α1D-adrenoceptor antagonist) all shifted the concentration–response curve for noradrenaline to the right, the rank order of potencies (apparent pA 2 values) being silodosin (9.32±0.11)>prazosin (8.55±0.10)>BMY-7378 (6.06±0.15). The α1A-adrenoceptor antagonist silodosin was thus much more effective than the α1D-adrenoceptor antagonist BYM-7378.

Conclusions: Our results demonstrate that in mouse ureters: the mRNA for the α1A-adrenoceptor was more prevalent than those for the α1B- and α1D-adrenoceptors, and that among these subtypes, the α1A-adrenoceptor plays the major role in noradrenaline-induced contraction.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Animals
  • Epinephrine / pharmacology
  • Gene Expression / physiology
  • Indoles / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Norepinephrine / pharmacology
  • Piperazines / pharmacology
  • Prazosin / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, alpha-1 / genetics*
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Ureter / drug effects
  • Ureter / physiology*

Substances

  • Adra1a protein, mouse
  • Adra1b protein, mouse
  • Adra1d protein, mouse
  • Adrenergic alpha-1 Receptor Antagonists
  • Indoles
  • Piperazines
  • RNA, Messenger
  • Receptors, Adrenergic, alpha-1
  • silodosin
  • BMY 7378
  • Norepinephrine
  • Prazosin
  • Epinephrine