LOCALIZATION OF THE ALPHA-1A-ADRENOCEPTOR IN THE HUMAN PROSTATE

Purpose: We determined the tissue localization of he 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 (I-125-Heat), and the alpha 1-antagonists WB-410 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl-1,40-dihydro-3-[N-(3-[4-hydroxy-4-phenylpiperidin-yl]propyl)]carboxamido-4-(4-nitrophenyl) (SNAP 5272, 3 x 10(-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. Results: Specific I-125-Heat binding associated with the epithelium and stroma were independently analyzed, WB-4101 and SNAP 5272 inhibited 100% of the specific I-125-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 I-125-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% of the specific I-125-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.