Human intestinal VIP receptor: cloning and functional expression of two cDNA encoding proteins with different N-terminal domains.
We describe here two human VIP receptor cDNA clones isolated from a jejunal epithelial cell cDNA library. The hIVR8 cDNA encodes a human VIP receptor consisting of 460 amino acids and has seven putative transmembrane domains like other G protein-coupled receptors. When expressed in COS-7 cells, hIVR8 conferred specific [125I]VIP binding sites (dissociation constant = 0.6 nM) with displacement patterns characteristic of the human common VIP/PACAP receptor, i.e., VIP = PACAP-27 > PACAP-38 > helodermin > growth hormone-releasing factor = peptide methionineamide > secretin. It also conferred stimulation of cAMP production by VIP (half-maximal stimulation for 0.5 nM peptide). Another clone, hIVR5, encodes a 495 amino acid VIP receptor-related protein exhibiting 100% homology with the functional VIP receptor (hIVR8) over the 428 amino acids at the C-terminus but a completely divergent 67 amino acid N-terminal domain. When expressed in COS-7 cells, this VIP receptor-related protein does not bind 125I-VIP, although it is normally addressed at the plasma membrane as assessed by immunofluorescence studies.
Couvineau
A
A
Unité de Neuroendocrinologie et Biologie Cellulaire Digestives, Institut National de la Santé et de la Recherche Médicale, Unité 410, Faculté de Médecine Xavier Bichat, Paris, France.
Rouyer-Fessard
C
C
Darmoul
D
D
Maoret
J J
JJ
Carrero
I
I
Ogier-Denis
E
E
Laburthe
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology
D018076:DNA, Complementary; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP