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

• Published in: Clinical science (1979) Vol. 96; no. 4; p. 397
• Main Authors: Okamoto-Koizumi, T, Takeda, M, Komeyama, T, Hatano, A, Tamaki, M, Mizusawa, T, Tsutsui, T, Obara, K, Tomita, Y, Arai, K, Takahashi, K
• Format: Journal Article
• Language: English
• Published: England 01-04-1999
• Subjects: 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
• ISSN: 0143-5221
• DOI: 10.1042/CS19980298

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.