Localization of the alpha 1A-adrenoceptor in the human prostate

J Urol. 1995 Dec;154(6):2096-9.

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 125iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (125I-Heat), and the alpha 1-antagonists WB-4101 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl-1,4-dihydro-3-[N-(3-[4-hydroxy-4-phenylpipe ridin- 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 125I-Heat binding associated with the epithelium and stroma were independently analyzed. WB-4101 and SNAP 5272 inhibited 100% of the specific 125I-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 125I-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 125I-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.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Dioxanes / pharmacology
  • Humans
  • Male
  • Piperidines / pharmacology
  • Prostate / chemistry*
  • Receptors, Adrenergic, alpha-1 / analysis*

Substances

  • Adrenergic alpha-Antagonists
  • Dioxanes
  • Piperidines
  • Receptors, Adrenergic, alpha-1
  • SNAP 5272
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane