Localization of the alpha 1A-Adrenoceptor in the Human Prostate

Abstract

Purpose We determined the tissue localization of the alpha 1a-adrenoceptor in the human prostate. Materials and Methods Autoradiographic localization of the alpha 1a-adrenoceptor in the human prostate was determined by performing competitive displacement experiments on slide mounted tissue sections using the ligand 125 iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (sup 125 I-Heat [dagger]), and the alpha 1-antagonists WB-4101 [double dagger] (4 X 10 sup -8 M.) and 5-carboxamido-2,6-diethyl-1,4-dihydro-3-[N- (3-[4-hydroxy-4-phenylpiperidin-yl]propyl)]carboxamido-4-(4-nitrophenyl) (SNAP 5272, [Section] 3 X 10 sup -7 M.). Under these experimental conditions, WB-4101 and SNAP 5272 are selective alpha 1a/alpha 1d-adrenoceptor and alpha 1a-adrenoceptor antagonists, respectively. The autoradiographs were quantitatively analyzed using a computer image analysis system. [dagger] New England Nuclear, Boston, Massachusetts. [double dagger] RBI, Natick, Massachusetts. [Section] Synaptic Pharmaceutical Corp., Paramus, New Jersey. Results Specific 125 I-Heat binding associated with the epithelium and stroma were independently analyzed. WB-4101 and SNAP 5272 inhibited 100 percent of the specific 125 I-Heat binding in the stroma, suggesting that all of the stromal alpha 1-adrenoceptors are of the alpha 1a subtype. WB-4101 inhibited none of the specific 125 I-Heat binding in the epithelium, suggesting that the alpha 1-adrenoceptor in the epithelium is of the alpha 1b subtype. SNAP 5272 displaced only 25 percent of the specific 125 I-Heat binding in the epithelium, suggesting that a relatively small percentage of the epithelial alpha 1-adrenoceptor is of the alpha 1a subtype. Conclusions To our knowledge, our study represents the first cellular localization of the alpha 1-adrenoceptor subtypes in the human prostate using highly selective alpha 1-adrenoceptor antagonists and is consistent with the physiological observation that the activity of prostatic smooth muscle is mediated by the alpha 1a-adrenoceptor.