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

Abstract

A B S T R A C TThe 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 nonselective ET receptor agonist ; 10 − 10 M to 10 − 6 M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3i10 − 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 concentrationresponse curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA 2 l 7.96 ; slope l 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.

Urinary Bladder Contraction and Relaxation: Physiology and Pathophysiology

“…Traish et al (661) also characterized the ET receptor subtypes in the rabbit bladder using radioligand binding and suggested that at least two subtypes exist in rabbit bladder tissue, ET-1 and ET-2 binding to one subpopulation (ET A ) and ET-3 to the other (ET B ). The main role of ET A receptors in the contractile effects of ETs in the detrusor has been confirmed by several other investigators in animal as well as human bladders (96,155,375,512). In human detrusor, Okamoto-Koizumi et al (512), using isometric contraction experiments and RT-PCR, demonstrated that the ET-1-induced contractions were mediated mainly by the ET A receptor and not by the ET B receptor.…”

Autoantibodies Directed Against the Endothelin A Receptor in Patients With Benign Prostatic Hyperplasia

“…Among the variety of pathogenic effects on prostate resulting from over‐stimulation of the endothelin—ETA axis, the most of these were discussed with respect to prostatic cancer , preferentially those focused to the vascular pathophysiology and cell growth could be also relevant for pathogenic processes in BPH/LUTS. After stimulation of the endothelin—ETA axis, as summarized in , animal and human detrusor muscle contracts whereby the ETA versus ETB mediated effect seems to be more pronounced . With respect to cell growth, antagonizing the endothelin—endothelin receptor axis inhibited detrusor and bladder smooth muscle cell growth .…”

The effect of endothelin‐1 on the production of interleukin‐6 in cultured human detrusor smooth muscle cells, and the effect of interleukin‐6 on the contractile response of bladder smooth muscle strips from rats

“…ET‐1 is one of the most potent vasoconstrictors known; it induces the contraction of isolated rabbit bladder and urethral SM [10], and of HDSM [11]. Urinary bladder synthesizes ET‐1 under conditions of BOO [1]; ET‐1 produced in this way plays a potential role in bladder hyperactivity [2].…”