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

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 3×10^-7 M. Neither IRL1620 nor sarafotoxin S6c (both ET_B-selective agonists; 10^-10 M to 10^-6 M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ET_A-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 ET_B-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 ET_A receptor mRNA fragment, but not ET_B. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ET_A receptor, not by the ET_B receptor.