Document Detail

Bradykinin, but not muscarinic, inhibition of M-current in rat sympathetic ganglion neurons involves phospholipase C-beta 4.
MedLine Citation:
PMID:  11050147     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2000-11-01     Completed Date:  2001-02-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  RC105     Citation Subset:  IM    
Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London, London, WC1E 6BT, United Kingdom.
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MeSH Terms
Bradykinin / metabolism*,  pharmacology
Cells, Cultured
Isoenzymes / genetics,  metabolism*
Muscarinic Antagonists / pharmacology*
Neurons / cytology,  drug effects,  enzymology*
Oligonucleotides, Antisense / pharmacology
Phospholipase C beta
Potassium Channel Blockers*
Potassium Channels / metabolism
RNA, Messenger / biosynthesis
Rats, Sprague-Dawley
Superior Cervical Ganglion / cytology,  drug effects,  enzymology
Type C Phospholipases / genetics,  metabolism*
Reg. No./Substance:
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 C beta; EC protein, rat; EC protein, rat; EC protein, rat; EC protein, rat

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