| Bradykinin, but not muscarinic, inhibition of M-current in rat sympathetic ganglion neurons involves phospholipase C-beta 4. | |
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MedLine Citation:
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PMID: 11050147 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rat superior cervical ganglion (SCG) neurons express low-threshold noninactivating M-type potassium channels (I(K(M))), which can be inhibited by activation of M(1) muscarinic receptors (M(1) mAChR) and bradykinin (BK) B(2) receptors. Inhibition by the M(1) mAChR agonist oxotremorine methiodide (Oxo-M) is mediated, at least in part, by the pertussis toxin-insensitive G-protein Galpha(q) (Caulfield et al., 1994; Haley et al., 1998a), whereas BK inhibition involves Galpha(q) and/or Galpha(11) (Jones et al., 1995). Galpha(q) and Galpha(11) can stimulate phospholipase C-beta (PLC-beta), raising the possibility that PLC is involved in I(K(M)) inhibition by Oxo-M and BK. RT-PCR and antibody staining confirmed the presence of PLC-beta1, -beta2, -beta3, and -beta4 in rat SCG. We have tested the role of two PLC isoforms (PLC-beta1 and PLC-beta4) using antisense-expression constructs. Antisense constructs, consisting of the cytomegalovirus promoter driving antisense cRNA corresponding to the 3'-untranslated regions of PLC-beta1 and PLC-beta4, were injected into the nucleus of dissociated SCG neurons. Injected cells showed reduced antibody staining for the relevant PLC-beta isoform when compared to uninjected cells 48 hr later. BK inhibition of I(K(M)) was significantly reduced 48 hr after injection of the PLC-beta4, but not the PLC-beta1, antisense-encoding plasmid. Neither PLC-beta antisense altered M(1) mAChR inhibition by Oxo-M. These data support the conclusion of Cruzblanca et al. (1998) that BK, but not M(1) mAChR, inhibition of I(K(M)) involves PLC and extends this finding by indicating that PLC-beta4 is involved. |
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Authors:
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J E Haley; F C Abogadie; J M Fernandez-Fernandez; M Dayrell; Y Vallis; N J Buckley; D A Brown |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 20 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2000 Nov |
Date Detail:
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Created Date: 2000-11-01 Completed Date: 2001-02-22 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: RC105 Citation Subset: IM |
Affiliation:
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Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London, London, WC1E 6BT, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bradykinin / metabolism*, pharmacology Cells, Cultured Isoenzymes / genetics, metabolism* Microinjections Muscarinic Antagonists / pharmacology* Neurons / cytology, drug effects, enzymology* Oligonucleotides, Antisense / pharmacology Phospholipase C beta Plasmids Potassium Channel Blockers* Potassium Channels / metabolism RNA, Messenger / biosynthesis Rats Rats, Sprague-Dawley Superior Cervical Ganglion / cytology, drug effects, enzymology Type C Phospholipases / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; 0/Muscarinic Antagonists; 0/Oligonucleotides, Antisense; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/RNA, Messenger; 58-82-2/Bradykinin; EC 3.1.4.-/Type C Phospholipases; EC 3.1.4.11/Phospholipase C beta; EC 3.1.4.11/Plcb1 protein, rat; EC 3.1.4.11/Plcb2 protein, rat; EC 3.1.4.11/Plcb3 protein, rat; EC 3.1.4.11/Plcb4 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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