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-[Nle 17]VIP, and tested their capacity to recognize recombinant rat- and human VIP 1- and VIP 2/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 VIP 1/PACAP receptors, the three lipophilic analogues had the same efficacy as VIP and [Nle 17]VIP. In preparations expressing the rat receptors, stearyl-[Nle 17]VIP had a lower efficacy than the other peptides tested. In preparations expressing a low level of VIP 1/PACAP receptors and in those expressing VIP 2/PACAP receptors, all analogues behaved like partial agonists. The lowest efficacy was observed for stearyl-[Nle 17]VIP on the VIP 2/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.
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