Cloning and expression of the human vasoactive intestinal peptide receptor

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.11.4986· OSTI ID:6056483

Sreedharan, S P; Robichon, A; Peterson, K E; Goetzl, E J ^[1]

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1. Univ. of California Medical Center, San Francisco (United States)

Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous systems. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activatingadenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in librares prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound {sup 125}I-labeled VIP specifically with a dissociation constant (K{sub d}) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound {sup 125}I-VIP from transfected COS-6 cells, with potencies in the order VIP > secretin = PHI >> glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hanster ovary K1 cells, indicing a 3-fold increase in the intracellular level of cAMP. The VIP receptor cloned exhibits {le}24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands.

• OSTI ID: 6056483
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:11; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
RECEPTORS
TISSUE DISTRIBUTION
RECOMBINANT DNA
DNA SEQUENCING
BRAIN
DNA-CLONING
HEART
INTESTINES
IODINE 125
KIDNEYS
LUNGS
PEPTIDES
PHOSPHORUS 32
RATS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM
CLONING
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISTRIBUTION
DNA
DNA HYBRIDIZATION
ELECTRON CAPTURE RADIOISOTOPES
GASTROINTESTINAL TRACT
HYBRIDIZATION
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques