title: Interaction of lipophilic VIP derivatives with recombinant VIP1/PACAP and VIP2/PACAP receptors.
abstract: Stearyl vasoactive intestinal polypeptide has been reported to be a VIP (vasoactive intestinal polypeptide) receptor agonist of high potency with an original bioavailability and action. We synthesized three fatty acyl derivatives, myristyl-, palmityl- and stearyl-[Nle17]VIP, and tested their capacity to recognize recombinant rat- and human VIP1- and VIP2/PACAP (pituitary adenylate cyclase-activating polypeptide) receptors and to stimulate adenylate cyclase activity. The three lipophilic analogues bound with high affinity (from 0.5 to 20 nM) to both receptor subtypes but did not distinguish between them. In preparations expressing a high density of human VIP1/PACAP receptors, the three lipophilic analogues had the same efficacy as VIP and [Nle17]VIP. In preparations expressing the rat receptors, stearyl-[Nle17]VIP had a lower efficacy than the other peptides tested. In preparations expressing a low level of VIP1/PACAP receptors and in those expressing VIP2/PACAP receptors, all analogues behaved like partial agonists. The lowest efficacy was observed for stearyl-[Nle17]VIP on the VIP2/PACAP receptor subclass. Based on our results, a complex pattern of in vivo biological effects of the lipophilic VIP derivatives should be expected: these compounds might behave as full agonists, partial agonists, or antagonists of the VIP response, depending on the number and the subtype of receptor expressed.
authors.affiliation: Department of Biochemistry and Nutrition, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gourlet
authors.forename: J
authors.initials: J
authors.lastname: Rathé
authors.forename: P
authors.initials: P
authors.lastname: De Neef
authors.forename: J
authors.initials: J
authors.lastname: Cnudde
authors.forename: M C
authors.initials: MC
authors.lastname: Vandermeers-Piret
authors.forename: M
authors.initials: M
authors.lastname: Waelbroeck
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C495401:ADCYAP1 protein, human; C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases