Receptors for Peptides of the VIP/PACAP and PYY/NPY/PP Families

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

“…1 is a prominent neuropeptide with wide distribution in both peripheral and central nervous systems and a large spectrum of biological actions in mammals (1,2). VIP-containing nerves and VIP effects have been described in digestive tract, cardiovascular system, airways, reproductive system, immune system, endocrine glands, and brain (1).…”

“…VIP-containing nerves and VIP effects have been described in digestive tract, cardiovascular system, airways, reproductive system, immune system, endocrine glands, and brain (1). Besides its short-term actions on exocrine secretions, hormone release, muscle relaxation, and metabolism (1,2), VIP has been also characterized as a growth regulator for fetuses and tumor cells and during embryonic brain development (3). There are recent evidences for an important role of VIP in the perception of pain (4) and suppression of inflammation (5).…”

“…There are recent evidences for an important role of VIP in the perception of pain (4) and suppression of inflammation (5). Finally, VIP has been involved in diseases such as the watery diarrhea syndrome and clinical applications of VIP have been already suggested in impotence, asthma, lung injury, a variety of tumors and neurodegenerative diseases (1)(2)(3).…”

“…VIP and PACAP are the most closely related peptides in terms of structure and function (2,6). They share two common receptors, VPAC 1 and VPAC 2 , which display high affinity for both VIP and PACAP (2,8).…”

“…This subfamily referred to as class II (2) also comprises receptors for parathyroid hormone, calcitonin, corticotropin-releasing factor, and the so called EGF-TM7 receptors (11). Class II family of receptors for peptides display several common properties including large N-terminal extracellular domains containing highly conserved cystein residues, N-terminal leader sequences, and complex gene organization with many introns (2).Although the structure-function relationship of VIP receptors, including VPAC 1 and VPAC 2 , has been recently documented (2,9,(12)(13)(14)(15)(16)(17)(18)(19)(20), the structure-function relationship of VIP itself is still poorly understood. Some old studies carried out before the characterization and cloning of VIP receptor subtypes (21-23) indicated that: (i) the entire sequence of VIP is required for full biological function (21, 22); (ii) VIP-related peptides having significant sequence homologies with VIP such as peptide histidine methionine amide, secretin, GRF, and helodermin behave as low potency VIP agonists (23); (iii) there are important differences between species in the pharmacology of VIP receptors, especially between rodents and humans (2, * The costs of publication of this article were defrayed in part by the payment of page charges.…”