GABA and dopamine act directly on melanotropes of Xenopus to inhibit MSH secretion

The release of melanophore stimulating hormone (MSH) from the pars intermedia of the amphibian Xenopus laevis is regulated by multiple factors of hypothalamic origin. The aim of this study was to determine if potential secretagogues function through a direct action on the melanotrope cell. For this purpose an in vitro superfusion system containing isolated melanotropes (cell suspension) was utilized. The viability of the cells in suspension was tested by examining their ability to synthesize, process and release pro-opiomelanocortin (POMC) related peptides. All biosynthetic functions appeared normal, with the exception that the isolated melanotropes are unable to N-terminally acetylate MSH. Release of immunoreactive-MSH from these cells was shown to be Ca2+-dependent, and high K+ stimulated release. Both the neurotransmitters dopamine and gamma-aminobutyric acid (GABA), which are thought to be physiologically important MSH-release inhibiting factors, were shown to inhibit MSH release from isolated melanotropes. Dopamine appeared to function through a dopamine D2 type receptor mechanism while for GABA, both a GABAa and GABAb receptor mechanism are involved.