M-15 - HIGH-AFFINITY CHIMERIC PEPTIDE THAT BLOCKS THE NEURONAL ACTIONS OF GALANIN IN THE HIPPOCAMPUS, LOCUS-CERULEUS, AND SPINAL-CORD

The 20-amino acid peptide M-15 binds with high affinity (IC50 almost-equal-to 0.1 nM) to I-125-labeled galanin (I-125-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace I-125-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11) amide] represents the first antagonist to the neuronal actions of GAL.