Effects of Chronic Treatment of Rats with Dopamine Receptor Drugs on the Post‐Translational Processing of Beta‐Endorphin in the Neurointermediate Lobe of the Pituitary Gland

Abstract

To investigate whether chronic changes in the activity of proopiomelanocortin cells in the neurointermediate lobe (NIL) of the pituitary gland are associated with changes in the enzymatic processing of 8-endorphin (BE), the effects of treatment of rats with the dopamine receptor antagonist haloperidol or the dopamine receptor agonist brornocriptine (2.5 mg.kg-sc, once daily for 21 days)were studied on the content of BE-related peptides in the NIL and on the release of these peptides from NILS in an in vitra superfusion system. Treatment with haloperidol increased, and with bromocriptine decreased the tissue content and the release of Na-acetyl-, B-, y-and a-endorphin-immunoreactivitp (ACE-, PE-, yE, and aE-IR). The endorphin-IR was further characterized using reversed-phase high-performance liquid chromatography and specific radioimmunoassay systems, and the following peptides were identified: des-tyrosine a-endorphin (DTaE), aE, ACME, yE, AcyE, PE-(1-31), AcBE-(1-31), AcPE-(1-27), AcBE-(1-26) and PE-(1-26)/pE-(1-27) (the latter peptides were not separated with the high-performance liquid chromatography system used). Analysis of NIL superfusates indicated that all peptides found in the tissue were released in vitro. In addition, an as yet unidentified acetylated IRendorphin component was found which was not observed in extracts of NIL tissue, and therefore was probably formed during release. Following haloperidol treatment, the levels of all PE-related peptides detected were increased in the tissues as well as superfusates, the increase in AcBE-(1-27) being most and that in PE-(1-26)lPE-(1-27) least pronounced. Following bromocriptine treatment, the concentrations of all peptides in tissues and superfusates were decreased as compared to vehicle controls. The acetylated endorphins, in particular AcPE-(1-27), were most affected and /?E-(1-26)/jE-(1-27) least affected. The results indicate that chronic modulation of the synthesizing and secretory activity of proopiornelanocortin cells in the NIL is parallelled by changes in the enzymatic processing of BE.