Alpha adrenoceptors in rat brain: direct identification with prazosin

Naunyn Schmiedebergs Arch Pharmacol. 1979 Sep;308(3):223-30. doi: 10.1007/BF00501386.

Abstract

Tritiated prazosin was used to characterize high affinity binding sites with characteristics similar to alpha 1 adrenoceptors in rat brain membranes. These sites were compared with alpha 2 adrenoceptors labeled with tritiated clonidine. The prazosin sites had an association constant of 2 nM-1 and bound to ligand optimal around pH 7.0. The density of the sites was 300 fmoles per mg of protein; the half time of dissociation of prazosin was 7 min at 30 degrees C. The order or potencies of agonists, determined from binding-inhibition experiments with labeled prazosin, was: naphazoline greater than clonidine greater than adrenaline greater than noradrenaline greater than phenylephrine greater than alpha-methylnoradrenaline greater than dopamine. The order of potencies of antagonists was: prazosin greater than phenoxybenzamine greater than phentolamine greater than clozapine greater than yohimbine. Sodium ions and divalent cations as well as guanyl nucleotides have little or no effect on the binding of the labeled antagonist. This is in contrast to the binding of the labeled agonist clonidine (Glossmann and Presek, 1979a, 1979b). Labeled prazosin may be a useful tool to characterize alpha 1 adrenoceptors.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Binding, Competitive / drug effects
  • Brain / drug effects*
  • Clonidine
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Membranes / metabolism
  • Prazosin*
  • Quinazolines*
  • Rats
  • Receptors, Adrenergic / drug effects*
  • Receptors, Adrenergic, beta / drug effects*
  • Sulfhydryl Reagents / pharmacology
  • Time Factors

Substances

  • Quinazolines
  • Receptors, Adrenergic
  • Receptors, Adrenergic, beta
  • Sulfhydryl Reagents
  • Clonidine
  • Prazosin