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 beta-endorphin (betaE), the effects of treatment of rats with the dopamine receptor antagonist haloperidol or the dopamine receptor agonist bromocriptine (2.5 mg.kg(-1) sc, once daily for 21 days) were studied on the content of betaE-related peptides in the NIL and on the release of these peptides from NILs in an in vitro superfusion system. Treatment with haloperidol increased, and with bromocriptine decreased the tissue content and the release of N(alpha)-acetyl-, beta-, gamma- and alpha-endorphin-immunoreactivity (AcE-, betaE-, gammaE, and alphaE-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 alpha-endorphin (DTalphaE), alphaE, AcalphaE, gammaE, AcgammaE, betaE-(1-31), AcbetaE-(1-31), AcbetaE-(1-27), AcbetaE-(1-26) and betaE-(1-26)/betaE-(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 IR-endorphin 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 betaE-related peptides detected were increased in the tissues as well as superfusates, the increase in AcbetaE-(1-27) being most and that in betaE-(1-26)/betaE-(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 AcbetaE-(1-27), were most affected and betaE-(1-26)/betaE-(1-27) least affected. The results indicate that chronic modulation of the synthesizing and secretory activity of proopiomelanocortin cells in the NIL is parallelled by changes in the enzymatic processing of betaE.
Sweep
C G
CG
Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, University of Utrecht, Vondellaan 6, 3521 GD Utrecht, The Netherlands.
Wiegant
V M
VM