PACAP Receptor

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid, C-terminally alpha-amidated peptide that can be isolated from an ovine hypothalamic extract based on its ability to stimulate cAMP formation in anterior pituitary cells. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-secretin-growth hormone-releasing hormone-glucagon superfamily. The sequence of PACAP has been remarkably well conserved during evolution, from protochordates to mammals. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and the respiratory and urogenital tracts. Two types of PACAP binding sites have been characterized: type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP, whereas type II binding sites have a similar affinity for both PACAP and VIP.
Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes: the PACAP-specific PAC1-R, which is coupled to several transduction systems, and the PACAP/VIP-indifferent VPAC1-R and VPAC2-R, which are primarily coupled to adenylyl cyclase. PAC1-Rs are particularly abundant in the brain, pituitary, and adrenal gland, whereas VPAC receptors are expressed mainly in the lung, liver, and testis^[1].