Chronic haloperidol treatment increases the level of in vitro translatable messenger ribonucleic acid coding for the beta-endorphin/adrenocorticotropin precursor proopiomelanocortin in the pars intermedia of the rat pituitary.
Chronic treatment of rats with haloperidol (1.5 mg/kg, once daily) over a period of 7--21 days resulted in a 80--100% increase in the tissue levels of immunoreactive beta-endorphin and in the in vitro release of immunoreactive beta-endorphin from the neurointermediate pituitary. Incorporation of [3H]phenylalanine into isolated neurointermediate pituitaries of haloperidol-treated rats revealed an increase in the amount of label incorporated into the beta-endorphin/ACTH precursor proopiomelanocortin (POMC) to a similar extent (about 80%) but had essentially no effect on the conversion of the precursor into beta-lipotropin and beta-endorphin. Extraction of messenger (m) RNA from neurointermediate pituitaries followed by cell-free translation in a reticulocyte system showed an increase in the total level of translatable mRNA (about 25%). The content of translatable mRNA coding for POMC, however, was increased by 100-150%. Time-course studies revealed a parallelism between the effect of haloperidol on the level of in vitro translatable mRNA coding for POMC and the ability of the drug to increase the concentrations of beta-endorphin in the neurointermediate pituitary. A complete reversal of the effects of haloperidol was seen 2 weeks after discontinuation of the drug. These findings suggest that the chronic blockade of dopaminergic receptors by haloperidol causes a reversible increase in the beta-endorphin biosynthesis in the rat intermediate pituitary at the pretranslational level by markedly increasing the level of translatable mRNA coding for POMC.
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis; D000818:Animals; D004723:Endorphins / Q000096:biosynthesis; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000096:biosynthesis*; D011333:Pro-Opiomelanocortin; D014176:Protein Biosynthesis / Q000187:drug effects; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D001615:beta-Endorphin
D004723:Endorphins; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D006220:Haloperidol