A heterogeneous population of alpha 1 adrenergic receptors mediates contraction of human corpus cavernosum smooth muscle to norepinephrine

J Urol. 1995 Jan;153(1):222-7. doi: 10.1097/00005392-199501000-00081.


In this study we investigated the physiological properties and binding characteristics of alpha-1 adrenergic receptor (alpha 1-AR) in human corpus cavernosum (HCC) in order to identify alpha 1-AR subtypes at the functional protein level. Exposure of tissue strips to norepinephrine (NE) caused concentration-dependent contractions that were partially and noncompetitively inhibited by 10 to 100 microM. of chloroethylclonidine (CEC), an alkylating agent that specifically and irreversibly inactivates alpha 1B-AR and alpha 1C-AR subtypes. Norepinephrine-induced contractions were competitively and effectively inhibited with WB 4101, a competitive, high-affinity antagonist for alpha 1A-AR and alpha 1C-AR subtypes. The CEC-insensitive receptor subtypes bound WB 4101 with high affinity, suggesting the presence of alpha 1A-AR in HCC. Binding of [3H]prazosin and 2-[beta-(4-hydroxy-3-[125I]iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) to membranes of HCC treated with or without CEC demonstrated the presence of two subpopulations: a CEC-sensitive receptor population (40 to 50%), which may represent inactivation of the alpha 1B-AR and alpha 1C-AR subtypes, and a CEC-resistant receptor subpopulation, which is probably the alpha 1A-AR subtype. The physiological and biochemical properties of alpha 1-AR in HCC clearly suggest that the NE-induced contraction of HCC smooth muscle is mediated by more than one alpha 1-AR subtype. It is likely that two or possibly three receptor subtypes are involved in mediating the contraction. Further, it is possible that NE-mediated contraction of trabecular smooth muscle requires synergistic receptor-receptor receptor interactions at the second messenger or at the receptor protein level.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkylating Agents / pharmacology
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Humans
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / pharmacology*
  • Penis / drug effects*
  • Penis / physiology*
  • Prazosin / metabolism
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / physiology*


  • Alkylating Agents
  • Receptors, Adrenergic, alpha-1
  • chlorethylclonidine
  • Clonidine
  • Norepinephrine
  • Prazosin