Function of M871 as a Galanin GAL2 Receptor Antagonist

2018-10-09

Introduction 

Galanin-(2–13)-Glu-His-(Pro)3-(Ala-Leu)2-Ala-amide (M871) is a novel peptide antagonist selectively recognizing the galanin receptor type 2. Galanin (GAL) and its three receptors have been linked to a wide variety of physiological processes and are distributed in both the central and peripheral nervous systems. Further knowledge of the properties of galanin-activated signaling systems can be obtained by the availability of peptide and non-peptide ligands that are selective for the different receptor subtypes. The current study describes binding and signaling data for the chimeric peptide, M871. This compound binds to the galanin receptor type 2 with more than 30-fold higher affinity than to the galanin receptor type 1 and exhibits antagonist actions at galanin receptor type 2, blocking increased release of inositol phosphate produced by galanin in CHO cells. This peptide opens new possibilities for the study of galanin receptor physiology.

Pharmacologic action

M871 block increased release of inositol phosphate produced by galanin in CHO cells. Signal transduction through GalR2 is examined by assessing the ability to stimulate IP production in CHO cells expressing GalR2. When treated with 0.01 μM rat galanin, the basal IP level increases with 70%, an effect that is completely abolished when the cells are treated with rat galanin in combination with M871 at the same concentration. This co-administration of peptide with galanin clearly blocks galanins' agonistic effect of producing IP following stimulation of GalR2; hence M871 acts in an antagonistic manner at GalR2 in vitro. Lower concentrations of M871 (0.001 and 0.0001 μM) also block the IP increase seen with galanin alone. M871 acts as an antagonist in the concentration range relevant for receptor studies.

Function

M871, which binds to the galanin receptors with over 30 times selectivity for GalR2 compared to GalR1. The displacement binding experiments are performed on human Bowes melanoma cells, which endogenously express GalR1, and CHO cells stably transfect to express human GalR2. M871 has been studied in an in vivo inflammatory pain model where the antagonistic action on GalR2 is supported further. Hence, M871 is the first galanin receptor subtype specific antagonistic peptide ligand published so far.

References:

Sollenberg, U. E., Lundström, L., Bartfai, T., & Langel, Ü. (2006). M871-a novel peptide antagonist selectively recognizing the galanin receptor type 2. International Journal of Peptide Research and Therapeutics, 12(2), 115-119.

Jimenez-Andrade, J. M., Lundström, L., Sollenberg, U. E., Langel, Ü., Castañeda-Hernandez, G., & Carlton, S. M. (2006). Activation of peripheral galanin receptors: differential effects on nociception. Pharmacology Biochemistry and Behavior, 85(1), 273-280.

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