title: The vasoactive intestinal peptide (VIP) receptor: recent data and hypothesis.
abstract: Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad range of biological activities in various tissues. After interaction with its membrane receptor, VIP generally induces a very large increase in the intracellular cyclic AMP level. Receptors for VIP have been described in numerous tissues and cell lines. The first results on VIP receptor structure have been obtained by covalent cross-linking using bifunctional reagents. The molecular mass of the different components characterized in this way differs greatly according to the species and the tissue used. This heterogeneity may reflect either a difference in the length of the cross-linked polypeptide backbone or differently glycosylated forms of the same polypeptide. The VIP binding site of intact human adenocarcinoma cells (HT29 cells) is an Mr 64,000 glycoprotein with 20kDa of N-linked oligosaccharide side chains containing sialic acid. The structure of the VIP binding site from HT29 cell is compared, first to the structure of the VIP receptor from other tissues, particularly that from rat liver, and second to the structure of the hepatic glucagon binding site. Recently, solubilization of the VIP receptor in an active form has provided a new way of studying this receptor. The HT29 cell line is an appropriate model to study the dynamics of the VIP receptor. After binding to its receptor, VIP is rapidly internalized, probably by receptor-mediated endocytosis. This internalization leads to a decrease in the cell surface receptor number and simultaneously to a homologous desensitization of adenylate cyclase. VIP is then degraded in the lysosomes, while most of the receptors are recycled back to the cell surface. The presence of an intracellular pool of unoccupied VIP receptors has been demonstrated after inactivation of the cell surface receptors by chymotrypsin. The kinetics of the receptor reappearance at the cell surface, after inactivation by chymotrypsin or after receptor-mediated endocytosis, indicate 2 possible intracellular pathways for occupied and unoccupied VIP receptors.
authors.affiliation: Institut de Chimie Biologique, Université de Provence, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Luis
authors.forename: J M
authors.initials: JM
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: el Battari
authors.forename: J
authors.initials: J
authors.lastname: Marvaldi
authors.forename: J
authors.initials: J
authors.lastname: Pichon
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D003034:Coated Pits, Cell-Membrane; D004705:Endocytosis; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D008970:Molecular Weight; D011964:Receptors, Gastrointestinal Hormone / Q000032:analysis* / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide; D012795:Sialoglycoproteins / Q000032:analysis; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D012795:Sialoglycoproteins; D014660:Vasoactive Intestinal Peptide; D005934:Glucagon; D000118:Acetylglucosaminidase; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase