Receptors for neuropeptide Y, γ-aminobutyric acid and dopamine differentially regulate Ca 2+ currents in Xenopus melanotrope cells via the G i protein β/γ-subunit

Abstract

Secretion of α-melanophore-stimulating hormone (αMSH) from pituitary melanotrope cells of the amphibian Xenopus laevis is under inhibitory synaptic control by three neurotransmitters produced by the suprachiasmatic nucleus: γ-aminobutyric acid (GABA), neuropeptide Y (NPY) and dopamine (DA). These inhibitory effects occur through G i-protein-coupled receptors (G iPCR), and differ in strength: GABA B-receptor-induced inhibition is the weakest, whereas DA (via a D 2-receptor) and NPY (via a Y 1-receptor) strongly inhibit, with NPY having a long-lasting effect. Previously it was shown that DA inhibits two (R- and N-type channel) of the four voltage-operated Ca 2+ channels in the melanotrope, and that only part of this inhibition is mediated by β/γ-subunits of the G i protein. We here demonstrate that also the Y 1- and GABA B-receptor inhibit only part of the total Ca 2+ current ( I Ca), with fast activation and inactivation kinetics. However, GABA B-mediated inhibition is weaker than the inhibitions induced via Y 1- and D 2-receptors (−21 versus −27% and −30%, respectively). Using a depolarizing pre-pulse protocol it was demonstrated that GABA B-induced inhibition of I Ca most likely depends on Gβ/γ-subunit activation whereas Y 1- and D 2- induced inhibitions are only partially mediated by Gβ/γ-subunits. No differences were found between the Y 1- and D 2-induced inhibitions. These results imply that activation of different G iPCR inhibits the I Ca through different mechanisms, a phenomenon that may underlie the different potencies of the suprachiasmatic neurotransmitters to inhibit αMSH secretion.