G protein preferences for dopamine D2 inhibition of prolactin secretion and DNA synthesis in GH4 pituitary cells

Abstract

Dopamine is the primary inhibitory regulator of lactotroph proliferation and prolactin (PRL) secretion in vivo, acting via dopamine D2 receptors (short D2S and long D2L forms). In GH4C1 pituitary cells transfected with D2S or D2L receptor cDNA, dopamine inhibits PRL secretion and DNA synthesis. These actions were blocked by pertussis toxin, implicating Gi/Go proteins. To address roles of specific Gi/Go proteins in these actions a series of GH4C1 cell lines specifically depleted of individual Gα subunits was examined. D2S-mediated inhibition of BayK8644-stimulated PRL secretion was primarily dependent on Go over Gi, as observed for BayK8644-induced calcium influx. By contrast, inhibitory coupling of the D2S receptor to TRH-induced PRL secretion was partially impaired by depletion of any single G protein, but especially Gi3. Inhibitory coupling of D2L receptors to PRL secretion required Go, but not Gi2, muscarinic receptor coupling was resistant to depletion of any Gi/Go protein, whereas the 5-HT1A and somatostatin receptors required Gi2 or Gi3 for coupling. The various receptors also demonstrated distinct G protein requirements for inhibition of DNA synthesis: depletion of any Gi/Go subunit completely uncoupled the D2S receptor, the D2L receptor was uncoupled by depletion of Gi2, and muscarinic and somatostatin receptors were resistant to depletion of Gi2 only. These results demonstrate distinct receptor-G protein preferences for inhibition of TRH-induced PRL secretion and DNA synthesis.