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

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.