Structural requirements for VIP interaction with specific receptors in human and rat intestinal membranes: effect of nine partial sequences.
Nine VIP sequences have been tested for their ability to inhibit the specific binding of 125I-VIP and to stimulate adenylate cyclase activity in intestinal epithelial membranes from rat and man. They are VIP 2-28; VIP 1-14; VIP 2-14; VIP 14-28; VIP 15-28; VIP 20-28; VIP 21-28 and two sequences where the N-terminal VIP 1-6 or VIP 1-9 have been joined covalently with the C-terminal VIP 20-28 or VIP 21-28. It appears that only VIP 2-28, VIP 14-28 and VIP 15-18 are able to inhibit competitively the binding of 125I-VIP to human and rat membranes. These analogues are respectively 88, 8,300 and 25,000 times less potent than VIP 1-28 in rat; they are respectively 70, 7,900 and 13,000 times less potent than VIP 1-28 in man. With respect to adenylate cyclase activation, VIP 14-28 and VIP 15-28 are very weak stimulators in the membranes from both species. VIP 2-28 behaves as a full VIP agonist in man whereas it is a partial VIP agonist in rat. These results indicate the structural importance of the whole VIP sequence for interacting with human and rat VIP receptors and further argue for a different structural requirement of rat and human receptors.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D013329:Structure-Activity Relationship; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases