DIFFERENTIAL ACTION OF SECRETO-INHIBITORS ON PROOPIOMELANOCORTIN BIOSYNTHESIS IN THE INTERMEDIATE PITUITARY OF XENOPUS-LAEVIS

In the South African clawed toad Xenopus laevis, background adaptation is regulated by alpha MSH, a POMC-derived peptide. After transfer of the animal from a black to a white background, secretion of alpha MSH from the intermediate pituitary lobe is inhibited by the hypothalamic neurotransmitter neuropeptide Y (NPY). The neurointermediate lobe in v itro is also subject to inhibitory regulation by dopamine and gamma-am inobutyric acid (GABA). In the nerve terminals contacting the intermed iate lobe of the pituitary, GABA is contained in electron-lucent vesic les, whereas dopamine and NPY coexist in electron-dense vesicles. To s tudy the role of these secrete-inhibitors in the regulation of POMC bi osynthesis, the rate of incorporation of radioactive amino acids into POMC protein was determined after in vitro treatment of the neurointer mediate pituitary with NPY, apomorphine (dopamine D-2 receptor agonist ), isoguvacine (GABA(A) receptor agonist), and baclofen (GABA(B) recep tor agonist). After 24 h of treatment, inhibition of POMC biosynthesis by NPY and apomorphine was 77% and 74%, respectively. Isoguvacine tre atment resulted in an inhibition of 59%, whereas no significant effect of baclofen was observed. When neurointermediate lobes were treated f or 3 days, inhibition of POMC biosynthesis by NPY was maintained, and inhibition by apomorphine was even stronger, whereas isoguvacine gave an inhibition of 52%, and baclofen produced 34% inhibition. Superfusio n experiments on alpha MSH secretion showed that prolonged treatment w ith the GABA receptor agonists results in a desensitization of GABA re ceptor-mediated signal transduction mechanisms, whereas the NPY recept or does not show desensitization. The observations indicate differenti al actions of the secrete-inhibitors NPY, apomorphine, and GABA agonis ts on POMC biosynthesis in the Xenopus intermediate pituitary, suggest ing a major role for dopamine and NPY, whereas GABA, acting via two re ceptor types, does not seem to have a major function in long term cont rol of POMC biosynthesis.