[3H]RX 781094: a new antagonist ligand labels alpha 2-adrenoceptors in the rat brain cortex.

[3H]RX 781094 [(imidazolinyl-2)-2 benzodioxane-1,4 [3H]chlorhydrate], a specific alpha 2-adrenoceptor antagonist radioligand, has been used to characterize alpha 2-adrenoceptors in rat cortical membranes. [3H]RX 781094 binding is reversible, saturable and stereospecific. It labels with high affinity a single population of non-interacting sites. The KD value was 3.9 +/- 0.4 nM and the Bmax 189.0 +/- 12.4 fmol/mg protein. Competition curves with different alpha-adrenoceptor agonists and antagonists showed that the binding sites labelled with [3H]RX 781094 had the pharmacological characteristics of alpha 2-adrenoceptors. Pretreatment with reserpine (2.5 mg/kg s.c., 24 h before the experiment) did not affect the KD or Bmax values of [3H]RX 781094 binding. Chemical destruction of noradrenergic pathways by systemic injection of DSP4 or intracerebral injection of 6-hydroxydopamine did not modify the KD or the Bmax of [3H]RX 781094 binding. It is concluded that the major proportion of alpha 2-adrenoceptors labelled with [3H]RX 781094 are not localised to noradrenergic nerve terminals.