Different regional distribution of the 5-HT reuptake complex, the 5-HT2A receptors and their second messenger IP3 in human brain.

The serotonin reuptake complex labelled with [3H]imipramine and [3H]paroxet ine, the 5-HT2A postsynaptic receptor labelled with [3H]ketanserin and the inositol trisphosphate (IP3) concentrations were simultaneously determined in several human brain regions. An inverse distribution was found between t he pre and postsynaptic receptors. Thus, while the serotonin reuptake compl ex labelled with either [3H]imipramine and [H-3]paroxetine displayed a maxi mum density in subcortical areas and basal ganglia, the 5-HT2A postsynaptic receptor labelled with [3H]ketanserin showed higher binding values in cort ical areas. The apparent affinity constants for the three radioligands were similar over the 12 regions studied (approx 1 nM for [3H] imipramine, appr ox 0.06 nM for [3H]paroxetine and approx 1 nM for [3H]ketanserin). IP3 levels were highest in frontal cortex (6.3 +/- 2.4 pmol/gr) followed by substantia nigra (4.6 +/- 15 pmol/gr). The remaining regions exhibited app roximately the same concentration range (two or three fold lower than front al cortex values). Frontal cortex was the only brain region showing a signi ficant correlation between the 5-HT2A maximum binding and the levels of its second messenger IP3.