Differential effects of coexisting dopamine, GABA and NPY on α-MSH secretion from melanotrope cells of Xenopus laevis

The secretion of α-MSH from the intermediate lobe of the pituitary gland of the amphibian Xenopus laevis is under complex neural control. Three neurotransmitters, dopamine, GABA and NPY, coexist in nerve terminals that contact the melanotrope cells. All three neurotransmitters inhibit α-MSH release. We have investigated the significance of this neurotransmitter coexistence for the regulation of α-MSH release, using an in vitro superfusion system. From experiments where lobes were treated with various combinations of receptor agonists we conclude that the transmitters act in an additive way but have clear, differential actions. Inhibition of secretion by either dopamine, isoguvacine (GABA<sub>A</sub> receptor agonist) or baclofen (GABA<sub>B</sub>receptor agonist) occurs rapidly and α-MSH secretion rapidly returns when treatment is terminated (recovery from baclofen being relatively fast, that from dopamine relatively slow); in contrast, inhibition by NPY and recovery from NPY-induced inhibition occurs only very slowly. Differential effects of the transmitters were also seen in experiments with 8-bromo-cyclic AMP, which strongly stimulates α-MSH secretion from isoguvacine- or baclofen-treated lobes, but is relatively ineffective in stimulating secretion from lobes treated with dopamine or NPY. NPY, furthermore, enables a short phasic stimulation of secretion by isoguvacine and attenuates the inhibitory action of dopamine and baclofen. Altogether it is concluded that the coexisting factors differentially affect the secretory process of the melanotrope cells of Xenopus laevis. NPY has a slow, sustained action whereas dopamine and GABA act fast