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Dopaminergic agents selectively alter the post-translational processing of beta-endorphin in the intermediate pituitary of the rat



Dopaminergic agents selectively alter the post-translational processing of beta-endorphin in the intermediate pituitary of the rat



Journal of Pharmacology and Experimental Therapeutics 243(1): 160-170



The present study examines whether sustained changes in the biosynthetic activity of the intermediate pituitary, induced pharmacologically by treating rats with dopamine receptor ligands, alters the post-translational processing of beta-endorphin (beta-END). Separation of the individual molecular forms of beta-END using ion exchange chromatography revealed that beta-END is processed to alpha-N-acetylated and nonacetylated forms of beta-END-(1-31), beta-END-(1-27) and beta-END-(1-26) in the neurointermediate lobe (NIL). Chronic treatment with D-2, but not D-1, dopamine receptor antagonists elevated total beta-END immunoreactivity (i beta-END) in the NIL but this increase was predominantly attributable to elevations in the concentrations of N-acetyl-beta-END-(1-31) and N-acetyl-beta-END-(1-27). In contrast, N-acetyl-beta-END-(1-26) was not significantly affected. The dopaminergic agonist, bromocriptine, had the opposite effect; it lowered total i beta-END levels, depleting N-acetyl-beta-END-(1-31) and N-acetyl-beta-END-(1-27) to a greater extent than N-acetyl-beta-END-(1-26). beta-END peptides were released in vitro in the same relative proportion as they were contained in the NIL suggesting that individual molecular forms of beta-END are not released preferentially. i gamma-END levels also were modulated by dopaminergic agents but the processing of gamma-END and alpha-END was not altered. Acute haloperidol treatment depleted i gamma-END levels but did not affect the pattern of beta-END peptides in the NIL. These results indicate that dopaminergic agents influence not only the secretion but also the post-translational processing of pituitary beta-END.

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Accession: 039863962

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PMID: 2959768


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