Characterization of the alpha(2)-adrenoceptor subtype, which functions as alpha(2)-autoreceptor in human neocortex

The pharmacological properties of the alpha(2)-adrenergic receptors regulat ing the release of norepinephrine were investigated in human neocortex. Sli ces were preincubated with [H-3]norepinephrine, superfused under blockade o f transmitter reuptake, and stimulated electrically. First, the autoinhibit ory circuit of [H-3]norepinephrine release was analyzed quantitatively by e stimation of the K-d of norepinephrine at the alpha(2)-autoreceptor (10(-7. 99) M), the concentration of the endogenous transmitter causing this autoin hibition at a stimulation frequency of 3 Hz (10(-7.61) M), and the maximum inhibition obtainable through the autoreceptor (83%). Second, antagonist pK (b) values of nine antagonists were determined by using their pEC(50) value s (negative logarithms of antagonist concentrations that increased the elec trically evoked overflow of tritium by 50%) against the release-inhibiting effect of the endogenous transmitter. When compared with binding or functio nal data from the literature, the pKb values correlated best with the antag onist affinities at alpha(2A) binding sites. In contrast, the correlations with alpha(2B), alpha(2C), and alpha(2D) sites were not as good. It is conc luded that in human neocortex prejunctional autoreceptors are alpha(2A).