EPIDERMAL GROWTH-FACTOR TREATMENT INDUCES D2 DOPAMINE-RECEPTORS FUNCTIONALLY COUPLED TO DELAYED OUTWARD POTASSIUM CURRENT (I-K) IN GH4C1 CLONAL ANTERIOR-PITUITARY-CELLS

GH4C1 cells, a clonal cell line from a rat pituitary tumor, have been widely used as a model to study the regulation of prolactin secretion. These cells, however, do not express dopamine D2 receptors and are th erefore not suitable for exploring mechanisms involved in dopamine inh ibition of prolactin secretion. The recent demonstration that epiderma l growth factor (EGF) is able to induce functional expression of D2 re ceptors in GH3 cells, a parental clonal cell line, overcomes this diff iculty. We have thus undertaken an electrophysiological study in order to check whether coupling of D2 receptors to K+ channels could be res tored in that model. Effects of dopamine on the non-inactivating volta ge-dependent outward K+ current (I-K) were investigated both in contro l and in EGF-treated GH4C1 cells. The K+ current was not modified by E GF treatment alone. In control cells, I-K measured before and during d opamine application was unchanged. In contrast, dopamine application m arkedly enhanced the K+ current in cells that had previously been expo sed to EGF. The effect was mimicked by the specific D2 receptor agonis t bromocriptine and blocked by sulpiride, a D2 receptor antagonist, th us indicating that the effect of dopamine was effectively due to the a ctivation of D2 receptors. These results bring further evidence that E GF-induced D2 receptors in clonal strains from rat pituitary tumors ar e functional and are coupled to the delayed outward K+ current I-K.