Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

Clin Sci (Lond). 1999 Apr;96(4):397-402.

Abstract

The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription-polymerase chain reaction (RT-PCR). ET-1 (a non-selective ET receptor agonist; 10(-10) M to 10(-6) M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3x10(-7) M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10(-10) M to 10(-6) M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10(-7) M to 10(-5) M) produced a marked shift to the right of the ET-1 concentration-response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2=7.96; slope=0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10(-7) M to 10(-5) M) had no effect on the ET-1 concentration-response curve. RT-PCR revealed positive amplification of ETA receptor mRNA fragment, but not ETB. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Azepines / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelin Receptor Antagonists
  • Endothelin-1 / pharmacology*
  • Endothelins / agonists
  • Endothelins / pharmacology
  • Gene Expression
  • Humans
  • Indoles / pharmacology
  • Isometric Contraction / drug effects*
  • Male
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Peptide Fragments / pharmacology
  • Receptors, Endothelin / genetics
  • Receptors, Endothelin / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism
  • Viper Venoms / pharmacology

Substances

  • Azepines
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Indoles
  • Peptide Fragments
  • Receptors, Endothelin
  • Viper Venoms
  • sarafotoxins s6
  • sovateltide
  • FR 139317