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Analogues of VIP, Helodermin, and PACAP Discriminate between Rat and Human VIP 1 and VIP 2 Receptors a
Author(s) -
GOURLET P.,
VANDERMEERS A.,
RAMPELBERGH J.,
NEEF P.,
CNUDDE J.,
WAELBROECK M.,
ROBBERECHT P.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb11184.x
Subject(s) - vasoactive intestinal peptide , receptor , secretin , secretin family , biology , endocrinology , medicine , neuropeptide , chemistry , biochemistry , secretion
A bstract : Vasoactive intestinal polypeptide (VIP) acts through interaction with two subclasses of seven transmembrane G protein‐coupled receptors named VIP 1 and VIP 2 receptors. These receptors have been cloned in different species, such as rat and human. Considering the different distribution of both receptor subclasses, there is considerable interest in the development of selective agonists and antagonists. The present study compares the binding properties of VIP, PACAP, GRF, secretin, and helodermin analogues on recombinant rat and human VIP 1 and VIP 2 receptors. On both rat and human receptors, secretin and GRF had a higher affinity for the VIP 1 receptor subtypes. The amino‐shortened VIP, and the carboxy terminal‐shortened VIP and PACAP analogues also presented a higher affinity for the VIP 1 receptor. PHI, PHV, helodermin, and helospectin were selective for the human VIP 2 receptor subtypes. These results suggest that the helical structure of the carboxy terminal end is necessary for VIP 2 recognition. The differences between species were the following: PHI, PHV, helodermin, and helospectin had a higher affinity for the rat VIP 1 receptor than for the human VIP 1 receptor. On both rat and human receptors, D‐Ala 4 VIP and D‐Phe 4 VIP had a high affinity for the VIP 1 receptor and a low affinity for the VIP 2 receptor. Thus, three domains of the ligand involved in VIP 1 /VIP 2 receptor discrimination were identified: the amino acid residue in position 4 ([D‐Ala 4 ], [D‐Phe 4 ]VIP), in positions 8 and 9 (the effects of helodermin and helospectin), and the carboxy terminal end (the effects of the shortened VIP and pituitary adenylate cyclase activating polypeptide analogues).