The hydrophobic amino acids in putative helix 8 in carboxy-terminus of histamine H3 receptor are involved in receptor-G-protein coupling

► Various mutations were introduced in helix 8 of H3R to examine its functional roles. ► Deletion of helix 8 abolished H3R-G-protein coupling and Gi-mediated signaling. ► Replacement of hydrophobic amino acids in helix 8 made H3R less activated. ► F7.60A was less responsive to both agonist and inverse agonist.