Secretion of alpha-melanophore-stimulating hormone (alphaMSH) from pituitary melanotrope cells of the amphibian Xenopus laevis is under inhibitory synaptic control by three neurotransmitters produced by the suprachiasmatic nucleus: gamma-aminobutyric acid (GABA), neuropeptide Y (NPY) and dopamine (DA). These inhibitory effects occur through G(i)-protein-coupled receptors (G(i)PCR), and differ in strength: GABA(B)-receptor-induced inhibition is the weakest, whereas DA (via a D2-receptor) and NPY (via a Y1-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 Ca2+ channels in the melanotrope, and that only part of this inhibition is mediated by beta/gamma-subunits of the G(i) protein. We here demonstrate that also the Y1- and GABA(B)-receptor inhibit only part of the total Ca2+ current (I(Ca)), with fast activation and inactivation kinetics. However, GABA(B)-mediated inhibition is weaker than the inhibitions induced via Y1- and D2-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 Gbeta/gamma-subunit activation whereas Y1- and D2- induced inhibitions are only partially mediated by Gbeta/gamma-subunits. No differences were found between the Y1- and D2-induced inhibitions. These results imply that activation of different G(i)PCR inhibits the I(Ca) through different mechanisms, a phenomenon that may underlie the different potencies of the suprachiasmatic neurotransmitters to inhibit alphaMSH secretion.