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Epidermal Growth Factor Promotes Uncoupling from Adenylyl Cyclase of the Rat D 2S Receptor Expressed in GH4C1 Cells
Author(s) -
Missale Cristina,
Boroni Flora,
Sigala Sandra,
Castelletti Laura,
Falardeau Pierre,
Toso Roberto,
Caron Marc G.,
Spano PierFranco
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62030907.x
Subject(s) - adenylyl cyclase , gs alpha subunit , epidermal growth factor , receptor , camp dependent pathway , medicine , g protein , endocrinology , signal transduction , adcy9 , microbiology and biotechnology , adcy10 , biology , transfection , chemistry , cell culture , biochemistry , genetics
In anterior pituitary cells or when transfected into host cell lines, the D 2 dopamine receptor inhibits adenylyl cyclase and activates potassium channels. The GH‐3 pituitary tumor cell line, which lacks functional D 2 receptors, responds to epidermal growth factor (EGF) by expressing a D 2 receptor that, paradoxically, couples to potassium channel activation but poorly inhibits adenylyl cyclase; this was correlated with a pronounced increase in α subunit of the G protein G 13 . In this study we have investigated the effects of EGF on the transduction mechanisms of D 2 receptors in GH4C1 cells transfected and permanently overexpressing the rat short D 2 receptor. Activation of D 2 receptors in these cells resulted in both inhibition of adenylyl cyclase and opening of potassium channels and inhibition of prolactin release by both cyclic AMP‐dependent and independent mechanisms. Exposure of the transfected GH4C1 cells to EGF caused a dramatic decrease in the coupling efficiency of the D 2 receptor to inhibit cyclic AMP‐dependent responses, leaving its activity toward potassium channels unchanged. The EGF treatment led to the concomitant increase in the membrane content of G 13 protein. These results suggest that the transmembrane signaling specificity of G protein‐coupled receptors can be modulated by the relative amounts of different G proteins at the cell membrane.