NEUROPEPTIDE-Y SUPPRESSES PROLACTIN SECRETION FROM RAT ANTERIOR-PITUITARY-CELLS - EVIDENCE FOR INTERACTIONS WITH DOPAMINE THROUGH INHIBITORY COUPLING TO CALCIUM-ENTRY

Expression elf neuropeptide Y (NPY) in the medial basal hypothalamus i s increased during lactation, and at least part of this increase is du e to the appearance of the peptide in hypothalamic tuberoinfundibular dopamine neurons, a cell population that does not exhibit NPY expressi on in other physiological conditions. The present studies tested the h ypothesis that NPY affects PRL secretion by modulating the action of d opamine (DA) at the lactotroph. In static incubations of cultured ante rior pituitary (AP) cells, the addition of either NPY or DA in concent rations of 0.1-500 nM resulted in dose-dependent inhibition of PRL sec retion, and the combination of DA and NPY in submaximal concentrations produced an additive inhibition of PRL release. NPY also inhibited PR L secretion induced by TRH in perifused AP cells, and the effects were again additive with DA. The interactions of NPY and DA on TRH-induced elevations in cytosolic Ca2+ ([Ca2+]i) were examined by loading cultu red AP cells of lactating rats with the fluorescent calcium probe fura -2. TRH produced a dose-dependent stimulation of [Ca2+]i, which was ch aracterized by a rapid transient spike and a more prolonged plateau. B oth phases were attenuated by either DA or NPY at 100 nM and were near ly abolished by the combination of DA and NPY, whereas neither DA nor NPY altered resting [Ca2+]i. DA and NPY also inhibited the increases i n PRL secretion and [Ca2+]i induced by elevated extracellular K+ in an additive manner. Stimulation of AP cells with TRH in the absence of e xtracellular Ca2+ resulted in an attenuated spike of PRL release and [ Ca2+]i and no plateau phase. Under these conditions, DA still inhibite d the residual [Ca2+]i and PRL responses, but the inhibitory effects o f NPY on PRL secretion and [Ca2+]i, and the potentiation by NPY of DA inhibition, were abolished. These results suggest that one physiologic al function of the NPY expressed in tuberoinfundibular dopamine neuron s in lactation is to amplify the inhibitory action of DA on PRL secret ion through negative coupling to the Ca2+ messenger system, particular ly the entry of extracellular Ca2+.