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Electrophysiological and molecular biological analysis on GABA_Breceptors in hypothalamic neuroendocrine cells

Research Project

Project/Area Number 09470020
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionUniversity of Occupational and Environmental Health

Principal Investigator

SHIBUYA Izumi  University of Occupational and Environmental Health Department of Physiology, Associate Professor, 医学部, 助教授 (50162649)

Co-Investigator(Kenkyū-buntansha) UEZONO Yasuhito  University of Occupational and Environmental Health Department of Pharmacology,, 医学部, 講師 (20213340)
UETA Yoichi  University of Occupational and Environmental Health Department of Physiology, Le, 医学部, 講師 (10232745)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥9,100,000 (Direct Cost: ¥9,100,000)
KeywordsGABA_B receptors / Patch clamp / supraoptic nucleus (SON) / Action Potentials / Excitatory Postsynaptic Currents / Inhibitory Postsynaptic Currents / Voltage-dependent Ca^<2+> currents / Xenopus oocytes / 神経内分泌ニューロン / baclofen / CFTR / GIRK / スライスパッチクランプ / シナプス電流 / 膜電位依存性Ca電流
Research Abstract

1)To elicidate the role of GABA_B receptors in the regulation of the magnocellular neurosecretory cells in the supraoptic nucleus (SON) of the hypothalamus, we measured the membrane potential, the firing frequency, and spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in rat SON slice preparations, and also the voltage-gated Ca^<2+> currents (VGC) of acutely dissociated rat SON neurons by the whole-cell patch-clamp technique. The selective GABAGABA_B agonist, baclofen suppressed the action potential discharge of SON neurons, without causing marked hyperpolarization. Baclofen educed the frequency of both the sEPSCs and sIPSCs without affecting the amplitude. The time constant of the decay phase of both the sEPSCs and sIPS Cs remained unchanged after baclofen application. The reduction of the frequency of the synaptic currents by baclofen was dose-dependent. Baclofen inhibited VGC also in a dose-dependent manner. Only the inhibition of N- and P/Q-types was significant. These results indicate that GABAGABA_B receptors are present both at the pre- and post-synaptic sites of SON neurons and mediate inhibition of EPSCs and IPSCs, and of N- and P/Q-type Ca^<2+> channels. These multiple inhibitory mechanisms mediated by pre- and postsynaptic GABAGABA_B receptors may play important roles in the regulation of SON neurons by the GABA neurons.
2)To investigate the signal transduction mechanism of GABAGABA_B receptor-mediated cellular responses, poly (A)^+ RNA derived from rat brain cortex was coexpressed with CFTR CI channls or with GIRK channels. We found that upon GABAGABA_B activation, the Gbetagamma released from PTX-sensitive G-proteins activates the adenylate cyclase type II, and this process requires Gs activation by Gs-coupled receptors. We also found that GABAGABA_B receptors activated the cloned GIRKs composed GIRK1 and GIRK2 as heteromultimers.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Kabashima, N. et al.: "Inhibition of spontaneous EPSCs and IPSCs by presynaptic GABA_B receptors on rat supraoptic magnocellular neurons." J.Physiol. (Lond.). 504(1). 113-126 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uezono, Y. et al.: "Enhancement by baclofen of the Gs-coupled receptor-mediated cAMP production in Xenopus oocytes expressing rat cerebral cortex poly (A)+RNA : a role of G-protein βγ subunits." Biochem.Biophys.Res.Comm.241(2). 476-480 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uezono, Y. et al.: "Activation of inwardly rectifying K^+ channels by GABA-B receptors expressed in Xenopus oocytes." Neuroreport. 9(4). 583-587 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harayama, N. et al.: "Inhibition of N-and P/Q-type calcium channels by postsynaptic GABA_B receptor activation in rat supraoptic neurones." J.Physiol. (Lond.). 509(2). 371-383 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ibrahim, N. et al.: "GABA_B receptor-mediated inhibition of spontaneous action potential discharge in supraoptic magocellular neurons of rats." Brain Res.813. 88-96 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I. et al.: "PACAP increases the cytosolic calcium concentration and stimulates somatodendritic vasopressin release in rat supraoptic neurons." J.Neuroendocrinol.10(1). 31-42 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, K. et al.: "PACAP causes Ca^<2+> release from ryanodine/caffeine stores through a novel pathway independent of both IP_3 and cAMP in bovine adreanl medullary cells." J.Neurochem.70(4). 1652-1661 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uezono, Y. et al.: "Adrenomedullin increases in intracellular Ca^<2+> and inositol 1, 4, 5-trisphosphate in human oligodendroglial cell line KG1C." Brain Res.786. 230-234 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hattori, Y., et al.: "Ionotropic and metabotropic glutamate receptor agonist-induced [Ca^<2+>]_i increase in isolated rat supraoptic neurones." J.Neuroendoclinol.10(5). 383-389 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I. et al.: "Patch-clamp analysis of PACAP-induced excitation in supraoptic neurones of rats." J.Neuroendoclinol.10(10). 759-768 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wang, Y.F. et al.: "Inhibition of spontaneous IPSCs by noradrenaline in rat supraoptic neurons through presynaptic α_2-adrenoceptors." Brain Res.807. 61-69 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I. et al.: "Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones." J.Physiol. (Lond.). 514(2). 351-367 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I. et al.: "The adrenal chromaffin cell" Hokkaido University Press, 75-87 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kabashima, N., Shibuya, I., Ibrahim, N., Ueta, Y.and Yamashita, H.: "Inhibition of spontaneous EPSCs and IPSCs by presynaptic GABA_B receptors on rat supraoptic magnocellular neurons." J.Physiol.(Lond.). 504. 113-126 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uezono, Y., Ueda, Y., Ueno, S., Shibuya, I., Toyohira, Y., Yanagihara, N., Yamashita, H.and Izumi, F.: "Enhancement by baclofen of the Gs-coupled receptor-mediated cAMP production in Xenopus oocytes expressing rat cerebral cortex poly (A)+RNA : a role of G-protein betagamma subunits." Biochem.Biophys.Res.Comm.241. 476-480 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uezono, Y., Akihara, M., Kaibara, M., Kuwano, C., Shibuya, I., Yanagihara, N., Yamashita, H.Taniyama, K.and Izumi, F.: "Activation of inwardly rectifyirng K^+ channels by GABA-B receptors expressed in Xenopus oocytes." Neuroreport. 9(4). 583-587 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harayama, N., Shibuya, I., Tanaka, K., Kabashima, N., Ueta.Y.and Yamashita, H.: "Inhibition of N-and P/Q-type calcium channels by postsynaptic GABA_B receptor activation in rat supraoptic neurones." J.Physiol.(Lond.). 509. 371-383 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ibrahim, N., Shibuya, I., Kabashima, N., Ueta.Y.and Yamashita, H.: "GABA_B receptor-mediated inhibition of spontaneous action potential discharge in supraoptic magocellular neurons of rats" Brain Res.813. 88-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I., Noguchi, J., Tanaka, K., Harayama, N., Inoue, Y., Kabashima, N., Ueta, Y., Hattori, Y.and Yamashita, H.: "PACAP increases the cytosolic calcium concentration and stimulates somatodendritic vasopressin release in rat supraoptic neurons." J.Neuroendocrinol.10. 31-42 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, K., Shibuya, I., Uezono, Y., Ueta, Y., Toyohira, Y., Yanagihara, N., Izumi, F., Kanno, T.and Yamashita, H.: "PACAP causes Ca^<2+> release from ryanodine/caffeine stores through a novel pathway independent of both IP_3 and cAMP in bovine adrenal medullary cells." J.Neurochem.70(4). 1652-1661 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uezono, Y., Shibuya, I., Ueda, Y., Tanaka, K., Toyohira, Y., Yanagihara, N., Yamashita, H.and Izumi, F.: "Adrenomedullin increases in intracellular Ca^<2+> and inositol 1,4,5-trisphosphate in human oligodendroglial cell line KG1C" Brain Res.786. 230-234 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hattori, Y., Shibuya, I., Tanaka, K., Kabashima, N., Ueta, Y.and Yamashita, H.: "Ionotropic and metabotropic glutamate receptor agonist-induced [Ca^<2+>]_i increase in isolated rat supraoptic neurones." J.Neuroendoclinol.10. 383-389 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I., Kabashima, N., Tanaka, K., Setiadji, V.S., Noguchi, J., Harayama, N., Ueta, Y.and Yamashita, H.: "Patch-clamp analysis of PACAP-induced excitation in supraoptic neurones of rats." J.Neuroendocrinol.10. 759-768 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wang, Y.F., Shibuya, I., Kabashima, N., Setiadji, V.S., Isse, T., Ueta Y., and Yamashita, H.: "Inhibition of spontaneous IPSCs by noradrenaline in rat supraoptic neurons through presynaptic alpha_2-adrenoceptors." Brain Res.807. 61-69 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I., Tanaka, K., Hattori, Y., Uezono, Y., Harayama, N., Noguchi, J., Ueta, Y., Izumi, F.and Yamashita, H.: "Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones." J.Physiol.(Lond.). 514. 351-367 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya, I., Tanaka, K., Ueta, Y., Nomura, M., Kanno, T.and Yamashita, H.: The mechanism of PACAP-induced Ca^<2+> mobilization in bovine adrenal chromaffin cells. In : The Adrenal Chromaffin Cell : Archetype and Exemplar of Cellular Signalling in Secretory Control.Ed.By Kanno, T., Nakazato, Y.and Kumakura, K.Hokkaido Univ.Press, 43-55 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ibrahim,N.et al.: "GABA_B receptor-mediated inhibition of spontaneous action potential discharge in supraoptic magocellular neurons of rats." Brain Res.813. 88-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al.: "Patch-clamp analysis of PACAP-induced excitation in supraoptic neurones of rats." J.Neuroendocrinol.10(10). 759-768 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,Y.F.et al.: "Inhibition of spontaneous IPSCsby noradrenaline in rat supraoptic neurons through presynaptic α_2-adrenoceptors." Brain Res.807. 61-69 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al.: "Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones." J.Physiol.(Lond.). 514(2). 351-367 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al.: "The adrenal chromaffin cell" Hokkaido University Press, 75-87 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kabashima,N.: "Inhibition of spontaneous EPSCs and IPSCs by presynaptic GABA_B receptors on rat supraoptic magnocellular neurons." J.Phyusiol.(Lond.). 503. 113-126 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uezono,Y.: "Enhancement by baclofen of the Gs-coupled receptor-mediated cAMP production in Xenopus oocytes expressing rat cerebral cortex poly(A)+RNA:a role of G-protein βγ subunits." Biochem.Biophys.Res.Comm.241. 476-780 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shibuya,I.: "PACAP increases the cytosolic calcium concentration and stimulates somatodendritic vasopressin release in rat supraoptic neurons." J.Neuroendocrinol.10. 31-42 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uezono,Y.: "Activation of inwardly rectifying K^+ channels by GABA-B receptors expressed in Xenopus oocytes." Neuroreport. 9(4). 538-587 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Harayama,N.: "Inhibition of N-and P/Q-type calcium channels by GABA_B receptor activation in rat supraoptic neurones." J.Physiol.(Lond.). (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,K.: "PACAP causes Ca^<2+> release from ryanodine/caffeine stores through a novel pathway independent of both IP_3 and cAMP in bovine adrenal medullary cells." J.Neurochem.(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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