Isolation and characterization of a hemoglobin-derived opioid peptide from the human pituitary gland.
An opioid nonapeptide was isolated from fresh frozen human pituitaries. Its primary structure (Leu-Val-Tyr-Pro-Trp-Thr-Gln-Arg) was identical to fragment 32-40 of the beta-, delta-, gamma- and epsilon-chains of human hemoglobin. A larger peptide of about 4.5 kDa, which generated a fragment containing the nonapeptide on trypsin digestion, showed an amino acid composition similar to fragment 1-41 of the beta-chain of human hemoglobin. The nonapeptide interacted with mu-opioid receptors in rat brain homogenates using [3H]-(D-Ala2, MePhe3, Gly-ol5)-enkephalin and with sigma-receptors using (+)-[3H]-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine, respectively. The affinities for mu-opioid receptors were in the same range as those observed for the structurally related beta-casomorphins. However, the isolated peptide showed markedly higher affinity at sigma-binding sites when compared to the beta-casomorphins or other opioid peptides. The opioid potency of this peptide as determined in the guinea-pig ileum myenteric plexus muscle preparation, was significant but less than that observed for the beta-casomorphins.
Glämsta
E L
EL
Department of Pharmacology, University of Uppsala, Sweden.
Marklund
A
A
Hellman
U
U
Wernstedt
C
C
Terenius
L
L
Nyberg
F
F
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004723:Endorphins / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism*
D000596:Amino Acids; D004723:Endorphins; D006454:Hemoglobins