Hirabayashi T, et al. - Researchers presented an overview of the history of the discovery of pituitary adenylate-cyclase-activating polypeptide (PACAP) and its three receptors. PACAP shows particularly high homology (~68%) to vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. Due to the high homology of the amino acid sequences of PACAP and VIP, these peptides share three class B-G-protein coupled receptors: the PAC1-Receptor (PAC1-R), the VPAC1-Receptor (VPAC1-R) and VPAC2-Receptor (VPAC2-R). As PACAP and its receptors are involved in diverse biological functions, understanding their signaling pathways could provide a help in the development of new therapeutic drugs.