Endothelin (ET) receptor subtypes in human prostate with benign prostatic hyperplasia were investigated by binding and functional studies. In the displacement experiment, LU224332 [endothelin-A/-B (ETA/ETB) nonselective antagonist] competed for [125I]ET-1 binding with a monophasic curve. On the other hand, LU135252 (ETA-selective antagonist) and sarafotoxin S6c (S6c, ETB-selective agonist) competed for [125I]ET-1 binding with shallow and biphasic curves. The analysis of the displacement curves for LU135252 and S6c showed that both ETA and ETB subtypes coexist but that ETA is the dominantly expressed receptor. In human prostate strips, 10 μM of both LU135252 and LU224332 strongly inhibited the contractile response to ET-1 with equal potency. However, 10 μM of BQ788 (ETB-selective antagonist) did not show a clear inhibition. S6c also produced a contractile response, which was potently inhibited by LU224332 or BQ788, and slightly suppressed by LU135252. These results suggest that in human prostate both ETA and ETB subtypes are functional receptors mediating contraction, but that ET-1-mediated contractions are predominantly mediated by activation of dominant receptor subtype, ETA
*Research and Development Division, Hokuriku Seiyaku Co. Ltd., Katsuyama, Fukui, †Experimental and Cardiovascular Research, Knoll AG, Ludwigshafen, Germany, and the Departments of ‡Urology and §Pharmacology, School of Medicine, Fukui Medical University, Matsuoka, Fukui, Japan
Address correspondence and reprint requests to Masafumi Oshita, Research and Development Division, Hokuriku Seiyaku Co. Ltd, Katsuyama, Fukui 911-8555, Japan. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.