Peptide fragment of the m3 muscarinic acetylcholine receptor activates G q but not G i2

G q , a heterotrimeric guanine nucleotide‐binding protein, plays important roles such as the regulation of calcium mobilization and cell proliferation. This protein is considered as a promising drug target for the treatment of cardiac hypertrophy. Selective activation of G q would be quite useful for analyzing the role of G q in signaling pathways. We synthesized m3i3c—a peptide with 16 amino acid residues that corresponds to the junction between the C ‐terminus of the third intracellular loop and the sixth transmembrane helix (TM‐VI) of human m3 muscarinic acetylcholine receptor, which couples to G q but not G i2 . At micromolar concentrations, this peptide was found to activate G q but not G i2 . This peptide is the first small compound that selectively activates G q but not G i2 . Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.