Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats

Br J Pharmacol. 2002 Apr;135(7):1757-64. doi: 10.1038/sj.bjp.0704639.


1. We have investigated the effects of chronic administration of prazosin (a subtype-nonspecific alpha-1 AR antagonist), KMD-3213 (an alpha-1A AR subtype-specific antagonist) and reserpine (a catecholamine depletor) on the density of alpha-1 AR subtypes in various rat tissues (liver, kidney, submaxillary gland, heart and spleen). 2. Administration of prazosin (2 mg kg(-1) day(-1), i.p.) for 2 weeks did not affect K(D) values for [(3)H]-prazosin or [(3)H]-KMD-3213 of alpha-1 ARs in five rat tissues tested. However, it caused 52% up-regulation of alpha-1B AR in the spleen, and 84% and 107% up-regulation of alpha-1A- and alpha-1B ARs, respectively, in the heart. Although major subtypes of alpha-1 AR are alpha-1A AR in the submaxillary gland, alpha-1B AR in the liver, and alpha-1A and alpha-1B ARs in the kidney, these tissues showed no up-regulation. The mRNA levels of alpha-1 AR subtypes were not affected by prazosin administration in any tissue tested. 3. Neither administration of KMD-3213 (2 mg kg(-1) day(-1), i.p.) nor reserpine (0.5 - 1 mg kg(-1) day(-1), i.p.) for 2 weeks caused any change in either the binding affinity for [(3)H]-prazosin or [(3)H]-KMD-3213 or the density of the alpha-1 AR subtypes in the five rat tissues. 4. Neither prazosin nor KMD-3213 treatment reduced the noradrenaline content in the five rat tissues, in contrast to reserpine treatment, which markedly reduced it. 5. The findings of the present study demonstrated that up-regulation of alpha-1 AR is selectively caused by prazosin treatment in some tissues but neither by KMD-3213 treatment nor by chemical denervation with reserpine. These results suggest that up-regulation of alpha-1 ARs is not caused by a simple blockade of sympathetic tone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Binding, Competitive
  • Indoles / pharmacology*
  • Male
  • Norepinephrine / metabolism
  • Polymerase Chain Reaction
  • Prazosin / pharmacology*
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / classification
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Reserpine / pharmacology
  • Tissue Distribution
  • Tritium
  • Up-Regulation


  • Adrenergic Uptake Inhibitors
  • Adrenergic alpha-Antagonists
  • Indoles
  • Receptors, Adrenergic, alpha-1
  • Tritium
  • Reserpine
  • silodosin
  • Norepinephrine
  • Prazosin