A bioactive peptide from the transmembrane 5-intracellular loop 3 region of the human 5HT1a receptor

15 amino acid peptide from the transmembrane 5-intracellular loop 3 region of the human 5HT1a receptor produced concentration-dependent decreases in agonist binding. This result is consistent with a competitive interaction between peptide, receptor, and G protein at the receptor-G protein interface. Bombesin and a 13 amino acid peptide from the carboxyl terminus region of the receptor were inactive. Additionally, the peptide decreased forskolin-mediated cAMP elevation. Overall, these results suggest that amino acid residues from this region of the receptor are involved in receptor-G protein coupling and that G protein is activated by the receptor.