Superactive lipophilic peptides discriminate multiple vasoactive intestinal peptide receptors

J Pharmacol Exp Ther. 1995 Apr;273(1):161-7.


To distinguish vasoactive intestinal peptide (VIP) receptors in the brain-mediating neurotransmission and neurotrophism, potent VIP analogues were designed. Using a single amino acid substitution and the addition of a fatty acyl moiety, an analogue was devised that exhibited both a 100-fold greater potency than VIP and specificity for a VIP receptor associated with neuronal survival. This VIP agonist increased neuronal survival via a cAMP-independent mechanism. Identical chemical modification of a prototype VIP antagonist (Met-Hybrid, Neurotensin6-11-VIP7-28) also resulted in a 100-fold greater potency in blocking VIP-mediated increases in neuronal survival. Blockade of circadian activity rhythms was limited to VIP antagonists that could inhibit VIP-mediated increases in cAMP. These lipophilic peptides provide novel tools in receptor discrimination and drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Circadian Rhythm / drug effects
  • Mice
  • Molecular Sequence Data
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vasoactive Intestinal Peptide / drug effects*
  • Spinal Cord / drug effects
  • Structure-Activity Relationship
  • Vasoactive Intestinal Peptide / analogs & derivatives
  • Vasoactive Intestinal Peptide / pharmacology*


  • Receptors, Vasoactive Intestinal Peptide
  • Vasoactive Intestinal Peptide