DOPAMINE ACTS ON ACETYLATION OF PROOPIOMELANOCORTIN-DERIVED PRODUCTS IN DOG PITUITARY

The effect of chronic dopaminergic receptor blockade using domperidone (DOM) on the immature dog pituitary content of POMC-related peptides was evaluated. Six immature dogs were treated with DOM for 15 days, 3 times/day, po (3 mg/kg) together with DOM sc (0.6 mg/kg) at 21.00 h. Placebo was administered to six control animals with the same protocol. On the 16th day, the animals were killed, the whole pituitary removed, homogenized, and submitted to reverse-phase HPLC purification prior to radioimmunoassay (RIA) evaluation of beta-endorphin, ACTH and alpha-MSH immunoreactivities (ir). DOM-treated dogs showed a pituitary concentration of beta-EP and ACTH similar to the placebo-treated dogs. The total alpha-MSH ir was similar in both groups and distributed on two main peaks: one corresponding to alpha-MSH and another coeluting with des-acetyl-alpha-MSH [1-13(ACTH)NH2]. However, the percentage of alpha-MSH on total ir in DOM-treated dogs (15.4 +/- 2.6%) was lower than in controls (37.5 +/- 4.5%, P less than 0.01); the corresponding percentage of 1-13(ACTH)NH2 content was 63.0 +/- 3.8% vs 44.7 +/- 3.7%, (P less than 0.01). The alpha-MSH/1-13(ACTH)NH2 ratio was considerably decreased by the treatment (0.25 +/- 0.06 vs 0.89 + 0.15, P less than 0.01). Acetyl beta-EP-like ir was also lower in treated (38.4 + 5.4 fmol/mg) vs control (86.6 + 19.2 fmol/mg, P less than 0.05) animals. These data indicate that the dopaminergic system plays an important role in the control of acetylation processes of POMC-related peptides in the pituitary