Synthesis of porcine leumorphin and some of its biological activities.
The carboxy-terminal nonacosapeptide sequence of porcine preproenkephalin B contains the sequence of Leu-enkephalin at its amino terminus. The endogenous existence of this peptide, leumorphin, has not yet been proved. Synthesis of leumorphin was carried out by a solid-phase technique and the purity and structure of the synthetic peptide were confirmed. Synthetic porcine leumorphin exhibited a dose-dependent opiate effect (ED50 4.70 X 10(-9) M) on electrically stimulated contraction of the guinea pig ileum preparation. The potency was about 100 times as high as that of Leu-enkephalin. Leumorphin was less potent than dynorphin(1-13) (ED50 0.38 X 10(-9) M) but it was more active than beta h-endorphin (ED50 18 X 10(-9) M). The opiate activity was only partially reversed by naloxone. Intracisternal injection of synthetic leumorphin caused significant analgesia in mice (ED50 7.31 nmol/mouse). The potency was lower than that of beta h-endorphin (ED50 0.60 nmol/mouse) but higher than that of dynorphin(1-13) (ED50 16.10 nmol/mouse). Intracisternally injected leumorphin did not produce such a violent behavioral effect as did dynorphin(1-13), and it exhibited a mild sedative effect. The data supports the concept that leumorphin is a new type of opioid peptide and that the synthetic preparation will be useful for further biological and immunological studies on this peptide.
D000698:Analgesia; D000818:Animals; D001681:Biological Assay; D004399:Dynorphins; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007202:Indicators and Reagents; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000138:chemical synthesis* / Q000494:pharmacology; D013552:Swine; D001615:beta-Endorphin
D004723:Endorphins; D004745:Enkephalins; D007202:Indicators and Reagents; D009294:Narcotics; D010446:Peptide Fragments; D011498:Protein Precursors; D009270:Naloxone; D001615:beta-Endorphin; C026843:dynorphin (1-13); D004399:Dynorphins; C033660:preproenkephalin