0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Dopamine D 2-Receptor Activation Differentially Inhibits N- and R-Type Ca 2+ Channels in Xenopus Melanotrope Cells

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dopamine inhibits pituitary melanotrope cells of the amphibian Xenopus laevis through activation of a dopamine (D<sub>2</sub>) receptor that couples to a G<sub>i</sub> protein. Activated G<sub>i</sub> protein subunits are known to affect voltage-operated Ca<sup>2+</sup> currents (I<sub>Ca</sub>). In the present study we investigated which Ca<sup>2+</sup> currents are regulated by D<sub>2</sub>-receptor activation and which G<sub>i</sub> protein subunits are involved. Whole-cell voltage-clamp patch-clamp experiments from holding potentials (HPs) of –80 and –30 mV show that 28.6 and 36.9%, respectively, of the total I<sub>Ca</sub> was inhibited by apomorphin, a D<sub>2</sub>-receptor agonist. The inhibited current had fast activation and inactivation kinetics. From an HP of –80 mV, inhibition of N-type Ca<sup>2+</sup> currents with ω-conotoxin GVIA and R-type current by SNX-482 reduced the efficacy of the apomorphin-induced inhibition. From an HP of –30 mV this reduction for ω-conotoxin GVIA was still observed. Blocking L-type current by nifedipine or P/Q-type current by ω-agatoxin IVA did not affect apomorphin-induced inhibition at either HP. Our results imply that D<sub>2</sub>-receptor activation inhibits both N- and R-type Ca<sup>2+</sup> currents. Using a strong depolarizing pre-pulse partially reversed the inhibition of the total current by apomorphin. About 50% of this inhibition was achieved through interaction of Gβ/γ proteins, and this part of the inhibited I<sub>Ca</sub> had fast activating and inactivating kinetics. However, the other part of the current inhibited by D<sub>2</sub>-receptor activation may proceed through Gα-PKA phosphorylation.

          Related collections

          Most cited references 19

          • Record: found
          • Abstract: found
          • Article: not found

          Crosstalk between G proteins and protein kinase C mediated by the calcium channel alpha1 subunit.

          The modulation of voltage-dependent Ca2+ channels at presynaptic nerve terminals is an important factor in the control of neurotransmitter release and synaptic efficacy. Some terminals contain multiple Ca2(+)-channel subtypes (N and P/Q), which are differentially regulated by G-protein activation and by protein kinase C (PKC)-dependent phosphorylation. Regulation of channel activity by crosstalk between second messenger pathways has been reported although the molecular mechanisms underlying crosstalk have not been described. Here we show that crosstalk occurs at the level of the presynaptic Ca2(+)-channel complex. The alpha1 subunit domain I-II linker, which connects the first and second transmembrane domains, contributes to the PKC-dependent upregulation of channel activity, while G-protein-dependent inhibition occurs through binding of Gbetagamma to two sites in the I-II linker. Crosstalk results from the PKC-dependent phosphorylation of one of the Gbetagamma binding sites which antagonizes Gbetagamma-induced inhibition. The results provide a mechanism for the highly regulated and dynamic control of neurotransmitter release that depends on the integration of multiple presynaptic signals.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release

              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Direct interaction of G   with a C-terminal G  -binding domain of the Ca2+ channel  1 subunit is responsible for channel inhibition by G protein-coupled receptors

                Bookmark

                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2004
                May 2005
                25 May 2005
                : 80
                : 6
                : 368-378
                Affiliations
                aDepartment of Cellular Animal Physiology, Nijmegen Institute for Neurosciences, Radboud University Nijmegen, Nijmegen, The Netherlands, and bDepartment of Anatomy, University of Turin, Turin, Italy
                Article
                84144 Neuroendocrinology 2004;80:368–378
                10.1159/000084144
                15731569
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 6, Tables: 2, References: 29, Pages: 11
                Categories
                Original Paper

                Comments

                Comment on this article