DIFFERENTIAL-EFFECTS OF COEXISTING DOPAMINE, GABA AND NPY ON ALPHA-MSH SECRETION FROM MELANOTROPE CELLS OF XENOPUS-LAEVIS

The secretion of alpha-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 te rminals that contact the melanotrope cells. All three neurotransmitter s inhibit alpha-MSH release. We have investigated the significance of this neurotransmitter coexistence for the regulation of alpha-MSH rele ase, using an in vitro superfusion system. From experiments where lobe s were treated with various combinations of receptor agonists we concl ude that the transmitters act in an additive way but have clear, diffe rential actions. Inhibition of secretion by either dopamine, isoguvaci ne (GABA(A) receptor agonist) or baclofen (GABA(B) receptor agonist) o ccurs rapidly and alpha-MSH secretion rapidly returns when treatment i s 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 eff ects of the transmitters were also seen in experiments with 8-bromo-cy clic AMP, which strongly stimulates alpha-MSH secretion from isoguvaci ne- or baclofen-treated lobes, but is relatively ineffective in stimul ating secretion from lobes treated with dopamine or NPY. NPY, furtherm ore, enables a short phasic stimulation of secretion by isoguvacine an d attenuates the inhibitory action of dopamine and baclofen. Altogethe r it is concluded that the coexisting factors differentially affect th e secretory process of the melanotrope cells of Xenopus laevis. NPY ha s a slow, sustained action whereas dopamine and GABA act fast.