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Signalling pathway of nitric oxide in synaptic GABA release in the rat paraventricular nucleus.
J Physiol. 2004 Jan 01; 554(Pt 1):100-10.JP

Abstract

In the paraventricular nucleus (PVN) of the hypothalamus, nitric oxide (NO) inhibits sympathetic outflow through increased GABA release. However, the signal transduction pathways involved in its action remain unclear. In the present study, we determined the role of cGMP, soluble guanylyl cyclase, and protein kinase G in the potentiating effect of NO on synaptic GABA release to spinally projecting PVN neurones. The PVN neurones were retrogradely labelled by a fluorescent tracer injected into the thoracic spinal cord of rats. Whole-cell voltage-clamp recordings were performed on labelled PVN neurones in the hypothalamic slice. Bath application of the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), reproducibly increased the frequency of miniature GABAergic inhibitory postsynaptic currents (mIPSCs) without changing the amplitude and the decay time constant. Neither replacement of Ca2+ with Co2+ nor application of Cd2+ to block the Ca2+ channel altered the effect of SNAP on mIPSCs. Also, the effect of SNAP on mIPSCs was not significantly affected by thapsigargin, a Ca2+-ATPase inhibitor that depletes intracellular Ca2+ stores. Application of a membrane-permeant cGMP analogue, pCPT-cGMP, mimicked the effect of SNAP on mIPSCs in the presence of a phosphodiesterase inhibitor, IBMX. Furthermore, both the soluble guanylyl cyclase inhibitor, ODQ, and the specific protein kinase G inhibitor, Rp pCPT cGMP, abolished the effect of SNAP on mIPSCs. Thus, these data provide substantial new information that NO potentiates GABAergic synaptic inputs to spinally projecting PVN neurones through a cGMP-protein kinase G pathway.

Authors+Show Affiliations

Department of Anaesthesiology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14678495

Citation

Li, De-Pei, et al. "Signalling Pathway of Nitric Oxide in Synaptic GABA Release in the Rat Paraventricular Nucleus." The Journal of Physiology, vol. 554, no. Pt 1, 2004, pp. 100-10.
Li DP, Chen SR, Finnegan TF, et al. Signalling pathway of nitric oxide in synaptic GABA release in the rat paraventricular nucleus. J Physiol (Lond). 2004;554(Pt 1):100-10.
Li, D. P., Chen, S. R., Finnegan, T. F., & Pan, H. L. (2004). Signalling pathway of nitric oxide in synaptic GABA release in the rat paraventricular nucleus. The Journal of Physiology, 554(Pt 1), 100-10.
Li DP, et al. Signalling Pathway of Nitric Oxide in Synaptic GABA Release in the Rat Paraventricular Nucleus. J Physiol (Lond). 2004 Jan 1;554(Pt 1):100-10. PubMed PMID: 14678495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signalling pathway of nitric oxide in synaptic GABA release in the rat paraventricular nucleus. AU - Li,De-Pei, AU - Chen,Shao-Rui, AU - Finnegan,Thomas F, AU - Pan,Hui-Lin, PY - 2003/12/18/pubmed PY - 2004/4/7/medline PY - 2003/12/18/entrez SP - 100 EP - 10 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 554 IS - Pt 1 N2 - In the paraventricular nucleus (PVN) of the hypothalamus, nitric oxide (NO) inhibits sympathetic outflow through increased GABA release. However, the signal transduction pathways involved in its action remain unclear. In the present study, we determined the role of cGMP, soluble guanylyl cyclase, and protein kinase G in the potentiating effect of NO on synaptic GABA release to spinally projecting PVN neurones. The PVN neurones were retrogradely labelled by a fluorescent tracer injected into the thoracic spinal cord of rats. Whole-cell voltage-clamp recordings were performed on labelled PVN neurones in the hypothalamic slice. Bath application of the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), reproducibly increased the frequency of miniature GABAergic inhibitory postsynaptic currents (mIPSCs) without changing the amplitude and the decay time constant. Neither replacement of Ca2+ with Co2+ nor application of Cd2+ to block the Ca2+ channel altered the effect of SNAP on mIPSCs. Also, the effect of SNAP on mIPSCs was not significantly affected by thapsigargin, a Ca2+-ATPase inhibitor that depletes intracellular Ca2+ stores. Application of a membrane-permeant cGMP analogue, pCPT-cGMP, mimicked the effect of SNAP on mIPSCs in the presence of a phosphodiesterase inhibitor, IBMX. Furthermore, both the soluble guanylyl cyclase inhibitor, ODQ, and the specific protein kinase G inhibitor, Rp pCPT cGMP, abolished the effect of SNAP on mIPSCs. Thus, these data provide substantial new information that NO potentiates GABAergic synaptic inputs to spinally projecting PVN neurones through a cGMP-protein kinase G pathway. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/14678495/Signalling_pathway_of_nitric_oxide_in_synaptic_GABA_release_in_the_rat_paraventricular_nucleus_ L2 - https://doi.org/10.1113/jphysiol.2003.053371 DB - PRIME DP - Unbound Medicine ER -