Receptors for neuropeptide Y, gamma-aminobutyric acid and dopamine differentially regulate Ca2+ currents in Xenopus melanotrope cells via the G(i) protein beta/gamma-subunit.
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.
Zhang
Hongyan
H
Department of Cellular Animal Physiology, Institute for Neuroscience, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
Roubos
Eric W
EW
Jenks
Bruce G
BG
Scheenen
Wim J J M
WJ
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D004553:Electric Conductivity; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology*; D044388:GTP-Binding Protein gamma Subunits / Q000502:physiology*; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000502:physiology*; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000378:metabolism*
D015220:Calcium Channels; D018491:Dopamine Agonists; C118981:G-protein Beta gamma; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D009478:Neuropeptide Y; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D018080:Receptors, GABA-B; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D009074:Melanocyte-Stimulating Hormones; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D001418:Baclofen; D001058:Apomorphine; D002118:Calcium