Epidermal growth factor treatment induces D2 dopamine receptors functionally coupled to delayed outward potassium current (IK) 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 therefore not suitable for exploring mechanisms involved in dopamine inhibition of prolactin secretion. The recent demonstration that epidermal growth factor (EGF) is able to induce functional expression of D2 receptors in GH3 cells, a parental clonal cell line, overcomes this difficulty. We have thus undertaken an electrophysiological study in order to check whether coupling of D2 receptors to K+ channels could be restored in that model. Effects of dopamine on the non-inactivating voltage-dependent outward K+ current (IK) were investigated both in control and in EGF-treated GH4C1 cells. The K+ current was not modified by EGF treatment alone. In control cells, IK measured before and during dopamine application was unchanged. In contrast, dopamine application markedly enhanced the K+ current in cells that had previously been exposed to EGF. The effect was mimicked by the specific D2 receptor agonist bromocriptine and blocked by sulpiride, a D2 receptor antagonist, thus indicating that the effect of dopamine was effectively due to the activation of D2 receptors. These results bring further evidence that EGF-induced D2 receptors in clonal strains from rat pituitary tumors are functional and are coupled to the delayed outward K+ current IK.
Gardette
R
R
INSERM U159, Paris, France.
Rasolonjanahary
R
R
Kordon
C
C
Enjalbert
A
A
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D004553:Electric Conductivity; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D004815:Epidermal Growth Factor; D013469:Sulpiride; D011188:Potassium; D004298:Dopamine