Galanin receptor antagonists M40 and C7 block galanin-induced feeding

Two peptide antagonists of the galanin receptor, M40 (galanin[1-13]-Pro-Pro-[Ala-Leu]2-Ala amide) and C7 (galanin[1-13]-spantide amide), significantly inhibited galanin-induced consumption of a palatable wet cookie mash, when microinjected intraventricularly to satiated rats. Antagonists were effective at doses equimolar to or less than the active doses of galanin. Feeding induced by an overnight fast was not significantly different in rats microinjected with saline as compared to M40 or C7, at doses which inhibited galanin-induced feeding. The activity of the chimeric compound, C7, did not appear to be linked to the properties of its C-terminal spantide-like sequence, as C7 did not induce barrel rolling at doses which inhibited galanin-induced feeding. The IC50 for displacement of 125I-[Tyr26]-porcine galanin 1-29 binding in rat hypothalamic membranes was 15 nM for M40, and 0.2 nM for C7, as compared to 0.8 nM for unlabelled porcine galanin(1-29). These two structurally different galanin antagonists, both demonstrating antagonist activity in vivo in awake, behaving rats, provide promising tools for further analyses of the functional activity of galanin in the mammalian brain.