Preferential binding to delta-receptors of the enkephalin-like tetrapeptide Tyr-Ile-Phe-Val. Electrophysiological and conformation studies.
The technique of microiontophoresis was used to study the effects of leucine-enkephalin [( Leu]enkephalin) and the tetrapeptide Tyr-Ile-Phe-Val on spontaneous and evoked activity of guinea-pig hypothalamic neurons. The inhibitory effects of the tetrapeptide were similar to those of [Leu]enkephalin on some neurons. However, in other cases, [Leu]enkephalin was inhibitory whereas Tyr-Ile-Phe-Val was without effect. These data and the fact that naloxone caused a different antagonism of inhibitory effects by these two peptides suggest the existence of two types of opiate receptors on some hypothalamic neurons and that Tyr-Ile-Phe-Val preferentially binds to delta-receptors. Conformational features of Tyr-Ile-Phe-Val have been established by 1H-NMR spectroscopy and were found to be in accordance with the above considerations. The peptide has a peculiar folded conformation called gamma-turn. Due to the restricted flexibility of this structure, the aromatic moieties (Tyr and Phe) and the hydrophobic (Val) or hydrophilic (terminal NH2 and CO2H) parts are positioned in a specific spatial relationship which can be related to an optimal binding to delta-receptors.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004594:Electrophysiology; D004745:Enkephalins / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007031:Hypothalamus / Q000502:physiology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism*; D011487:Protein Conformation; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D009270:Naloxone; C044140:tyrosyl-isoleucyl-phenylalanyl-valine