Differential effects of the putative galanin receptor antagonists M15 and M35 on striatal acetylcholine release

The putative galanin receptor antagonists M15 and M35 were examined for their effects on the basal and the galanin-evoked release of acetylcholine in the striatum. Extracellular concentrations of acetylcholine were measured in male rats using in vivo microdialysis and high pressure liquid chromatography techniques. Galanin (300 microM or 3 nmol/10 microliters), perfused through the microdialysis membrane into the striatum, enhanced (100% increase) basal acetylcholine release. M35 (300 microM or 3 nmol/10 microliters) also stimulated the basal acetylcholine release to some extent (about 50%) while M15 at the same concentration failed to do so. When M15 and M35 were coinfused with galanin, the galanin-evoked acetylcholine release was blocked completely by M15 (300 microM or 3 nmol/10 microliters) but only partially by M35 (300 microM or 3 nmol/10 microliters). The increase in acetylcholine release induced by M35 (300 microM) was blocked by M15 (300 microM). It is concluded that M15 is a full galanin receptor antagonist while M35 behaves as a mixed agonist-antagonist in vivo in the rat striatum. Both M15 and M35 fully displaced 0.2 nM [125I]galanin from its binding sites in the striatal membranes. The Hill coefficient of these [125I]galanin displacement curves with M15 and M35 was 0.4-0.5 compared to unity in the case of galanin. Analysis of the displacement curves suggested that both M15 and M35 recognized two classes of galanin binding sites in striatal membranes of the rat. To explain the difference between M15 and M35 it is suggested that there may exist a putative subtype of galanin receptor in the striatum, which is differentially affected by M15 and M35.