Isolation of a novel tetrapeptide with opiate and antiopiate activity from human brain cortex: Tyr-Pro-Trp-Gly-NH2 (Tyr-W-MIF-1).
A novel tetrapeptide, Tyr-Pro-Trp-Gly-NH2 (Tyr-W-MIF-1), was purified from extracts of frontal cortex of human brain tissue by several consecutive reversed-phase high performance liquid chromatographic steps followed by a radioimmunoassay originally developed for Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1). Sequencing, mass spectrometric analysis, and comparison of its chromatographic behavior with that of the synthetic peptide confirmed the structure. Like Tyr-MIF-1, which was previously isolated from human brain tissue, Tyr-W-MIF-1 can inhibit the binding of 3H-DAMGO (selective for mu opiate receptors) to rat brain and can act as an opiate agonist as well as antagonist. Tyr-W-MIF-1 was a more potent opiate agonist than Tyr-MIF-1, the free acid of Tyr-W-MIF-1, and the structurally related hemoglobin-derived opiate peptide hemorphin-4 (Tyr-Pro-Trp-Thr) in the guinea pig ileum. Each of these peptides acted as opiate antagonists on the ileum from morphine-tolerant guinea pigs; the free acid of Tyr-W-MIF-1 was the most potent antagonist in inhibiting the activity of DAMGO. The results demonstrate the presence in human brain of a new member of the Tyr-MIF-1 family of biologically active peptides.
Erchegyi
J
J
VA Medical Center, New Orleans, LA 70146.
Kastin
A J
AJ
Zadina
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors*; D005625:Frontal Lobe / Q000737:chemistry*; D006168:Guinea Pigs; D006801:Humans; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects*; D009294:Narcotics / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D009479:Neuropeptides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D011863:Radioimmunoassay; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D004745:Enkephalins; D009294:Narcotics; D009479:Neuropeptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C077532:tyrosyl-prolyl-tryptophyl-glycinamide; D009075:MSH Release-Inhibiting Hormone