Endorphins are stored in biologically active and inactive forms: isolation of α-N-acetyl peptides

Smyth, Derek G.; Massey, D. E.; Zakarian, S.; Finnie, M. D. A.

doi:10.1038/279252a0

Cited by 278 publications

(62 citation statements)

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“…Each of the four porcine peptides was obtained pure after a second ion exchange step and characterized by amino acid analysis with acid or enzymic hydrolysis. The values obtained corresponded to the values given by authentic peptides that had been isolated in homogeneous form by other procedures (12). Close correlation was observed between the amounts of the four peptides determined by chromatography and immunoassay and the amounts determined by chromatography and amino acid analysis.…”

Section: Resultsmentioning

confidence: 61%

“…It might, of course, have an entirely different biological activity but so far there is no evidence for this. Similarly, the acetyl derivatives of the C-and C'-Fragments are inert as opiates (12). They are probably formed concomitantly with a-melanotropin because these acetylated peptides are concentrated in the same region of pituitary (this communication and ref.…”

Section: Discussionmentioning

confidence: 99%

“…LPH, the C-Fragment of LPH, the C'-Fragment, the acetyl derivatives of the C-and C'-Fragments, the nonadecapeptide (LPH-61-79), and corticotropin were obtained by extraction from porcine pituitary (12,15). Methionine enkephalin was prepared by synthesis.…”

Section: Methodsmentioning

confidence: 99%

“…All these peptides occur naturally, but previous studies on the distribution of ,B-endorphin by immunofluorescence (5,6) or by radioimmunoassay of tissue extracts after gel filtration (7)(8)(9)(10) have not differentiated between them. Because only the CFragment exhibits potent opiate activity-the C'-Fragment is '/5ooth as active as an analgesic agent (11) and the acetyl peptides (12) and LPH (13,14) are inert-it is essential that the immunoreactive peptides should be precisely identified. We give here a brief description of our detailed mapping of the pituitary and brain of the rat by immunofluorescence using antibodies raised against homogeneous porcine C-Fragment and we present the results of experiments that have allowed characterization of the fluorescing substances in specific regions.…”

mentioning

confidence: 99%

“…

ABSTRACT The recent isolation and identification of a-N-acetyl forms of the C-Fragment of lipotropin (fl-endorphin, residues 61-91) and the C'-Fragment (residues 61-87) [Smyth, D. G., Massey, D. E., Zakarian, S. & Finnie, M. (1979) Nature (London) 279, 252-254] has led to a study of their distribution in the pituitary and brain of the rat. Regions were mapped by the method of immunofluorescent staining and the reactive peptides were determined by immunoassay after extraction, gel filtration, and ion exchange chromatography.

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mentioning

confidence: 99%

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Distribution of active and inactive forms of endorphins in rat pituitary and brain.

Zakarian¹,

Smyth²

1979

Proc. Natl. Acad. Sci. U.S.A.

143

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The recent isolation and identification of a-N-acetyl forms of the C-Fragment of lipotropin (fl-endorphin, residues 61-91) and the C'-Fragment (residues 61-87) [Smyth, D. G., Massey, D. E., Zakarian, S. & Finnie, M. (1979) Nature (London) 279, 252-254] has led to a study of their distribution in the pituitary and brain of the rat. Regions were mapped by the method of immunofluorescent staining and the reactive peptides were determined by immunoassay after extraction, gel filtration, and ion exchange chromatography. The major immunoreactive peptides in both lobes of the pituitary were found to be C'-Fragment and N-acetyl C'-Fragment, which are weakly active or inactive as opiates; the C-Fragment and its N-acetyl derivative represented minor components. This indicates that in the rat the circulating "endorphins" released from pituitary would have little morphinomimetic activity. The same four immunoreactive peptides were observed in rat brain. In the hippocampus the C'-Fragment was the principal component; in the midbrain there was more C-Fragment but C'-Fragment predominated; in the hypothalamus the C-Fragment was the major peptide, almost to the exclusion of the other peptides. The results demonstrate that the processing of lipotropin is under differential control in anatomically distinct regions of the central nervous system. The processing of lipotropin in the hypothalamus is directed specifically to the production of lipotropin C-Fragment.Understanding of the full physiological role of the endorphins must start from the identification of these peptides and elucidation of their distribution in regions of pituitary and brain. Present in picomolar concentrations, they can be detected and measured by the application of highly sensitive immunological techniques involving the use of specific antibodies. In studies of f3-endorphin [lipotropin (LPH) C-Fragment] the antisera employed have exhibited COOH-terminal specificity (1-4) and would react with the a-N-acetyl derivatives of the C-and C'-Fragments of LPH, as well as with a series of peptides including the 31,000-Mr endorphin prohormone, LPH, the C-Fragment (residues , and the C'-Fragment (residues 61-87). All these peptides occur naturally, but previous studies on the distribution of ,B-endorphin by immunofluorescence (5, 6) or by radioimmunoassay of tissue extracts after gel filtration (7-10) have not differentiated between them. Because only the CFragment exhibits potent opiate activity-the C'-Fragment is '/5ooth as active as an analgesic agent (11) and the acetyl peptides (12) and LPH (13,14) are inert-it is essential that the immunoreactive peptides should be precisely identified. We give here a brief description of our detailed mapping of the pituitary and brain of the rat by immunofluorescence using antibodies raised against homogeneous porcine C-Fragment and we present the results of experiments that have allowed characterization of the fluorescing substances in specific regions. The data reveal strikingly different patterns of distribution of ...

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Section: Resultsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%