Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a polypeptide hormone which stimulates adenylate cyclase in pituitary cells. Two forms of PACAP are known, one of 38 amino acids (PACAP-38) and a C-terminally truncated form of 27 amino acids (PACAP-27). PACAP-27 has an amino acid sequence identity of 68% with vasoactive intestinal polypeptide (VIP) and of 37% with secretin, indicating that PACAP is a member of the VIP/secretin/glucagon family. PACAP is present not only in various areas of the central nervous system including the hypothalamus, cerebral cortex, hippocampus and posterior pituitary, but also in peripheral tissues such as the testis, adrenal gland and gut, and seems to function as a neuromodulator or neurotransmitter in the central and peripheral nervous systems. PACAP exerts its actions through G-protein linked membrane receptors. Recently, three receptor subtypes have been cloned : PACAP receptor is a PACAP-preferring receptor, while VIP receptor and VIP2 receptor exhibit similar affinities for PACAP and VIP. Together with receptors for secretin, glucagon, glucagon-like peptide 1, growth hormone-releasing factor, calcitonin, and parathyroid hormone/parathyroid hormone-related peptide they constitute a subfamily of the Gs protein-coupled receptors. The PACAP-R gene has recently been isolated. The gene contained alternative exons which are processed by different splicing and give isolated. the gene contained alternative exons which are processed by different splicing and give rise to several receptor variants. Expression of these variants revealed altered properties of ligand binding and cAMP and phosphatidylinositol production. The distribution of the PACAP and VIP receptor mRNAs was examined in rat tissues by Northern hybridization and in situ hybridization. The distribution of PACAP receptor mRNA differed considerably from, though partly overlapped, that of VIP receptor mRNA, suggesting that these receptors have different functions. Possible roles that these receptors might play were discussed.
