Characterization of proenkephalin B-derived opioid peptides in the human hypothalamo-neurohypophyseal axis.
Proenkephalin B-derived opioid peptides, such as dynorphin1-17, dynorphin1-8, dynorphin B, alpha-neo-endorphin and beta-neo-endorphin in the human hypothalamo-neurohypophyseal tract were quantitated and characterized by the combined use of various radioimmunoassays, gel filtration, high performance liquid chromatography and enzymatic cleavage. Chromatographic analysis of immuno-reactive peptide levels determined that, in each case, these were comprised almost exclusively of the authentic peptides both in the neurohypophysis and hypothalamus. Concentrations of authentic proenkephalin B-peptides were 100-5000-fold lower in the human as compared to the rat neurohypophysis. However, in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and certain other nuclei of the human hypothalamus concentrations of authentic peptides were found to be in the same range as those in the rat hypothalamus. The ratio of proenkephalin B-peptides in PVN and SON to those of the neurohypophysis in the rat was ca. 1:50. Conversely, in man these ratios were shown to be 80:1 for dynorphin B, 6:1 for alpha-neo-endorphin and 1:1 for all other peptides evaluated. Examination of postmortem degradation of peptides indicated that these lower levels in the neurohypophysis are not due to a higher rate of postmortem breakdown. Since levels of both vasopressin and beta-endorphin were very high, these deficits in proenkephalin B-peptides were selective and do not represent a generalized property of the human pituitary. Experiments involving enzymatic cleavage demonstrated the occurrence of higher molecular weight forms containing the Leu-enkephalin sequence which were not recognized by the antisera employed.(ABSTRACT TRUNCATED AT 250 WORDS)
Arendt
R M
RM
Seizinger
B R
BR
Pasi
A
A
Mehraein
P
P
Herz
A
A
D000818:Animals; D004399:Dynorphins / Q000032:analysis; D004723:Endorphins / Q000032:analysis*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000032:analysis*; D007033:Hypothalamus, Middle / Q000032:analysis; D010286:Paraventricular Hypothalamic Nucleus / Q000032:analysis; D010903:Pituitary Gland, Anterior / Q000032:analysis; D010904:Pituitary Gland, Posterior / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D051381:Rats; D013377:Substantia Innominata / Q000032:analysis; D013495:Supraoptic Nucleus / Q000032:analysis
D004723:Endorphins; D011498:Protein Precursors; D004399:Dynorphins