ENDOTHELIN-1 IN THE HUMAN PROSTATE - TISSUE-LEVELS, SOURCE OF PRODUCTION AND ISOMETRIC TENSION STUDIES

Endothelins mediate contractile responses in many types of vascular an d nonvascular smooth muscle. The present study represents the first de tailed characterization of endothelins in the human prostate. The obje ctives of this study were to determine the tissue levels and source of endogenous endothelin-1 (ET1) in the human prostate. The contractile effects of ET1 were also investigated using in vitro isometric tension studies. The mean tissue level of ET1 was 0.58 +/- 0.08 pg./mg. tissu e wet weight. Endothelin-like activity was markedly prominent in the g landular epithelium of the human prostate, whereas minimal endothelin- like activity was observed in the prostatic stroma. Strips of human pr ostatic tissue were suspended in isolated tissue chambers and challeng ed to a concentration response of ET1. The mean EC50 and E(max) for ET 1 was 3.2 X 10(-8) M. and 0.12 +/- 0.02 gm. force per mm.2 cross-secti onal area (CSA), respectively. Preincubation with indomethacin, terazo sin, or nifedipine did not alter the concentration-dependent response to ET1. A calcium-free buffer abolished the contractile response to ET 1. Thus, ET1 mediates a potent contraction of human prostatic smooth m uscle that is not mediated via alpha1 adrenergic or dihydropyridine se nsitive calcium channels or prostaglandin synthesis. The presence of m arked endothelin-like immunoreactivity strongly suggests a biological significance for endogenous endothelins in the human prostate.