Document Detail

Role of TRPV1 and intracellular Ca2+ in excitation of cardiac sensory neurons by bradykinin.
MedLine Citation:
PMID:  17491115     Owner:  NLM     Status:  MEDLINE    
Bradykinin is an important mediator produced during myocardial ischemia and infarction that can activate and/or sensitize cardiac spinal (sympathetic) sensory neurons to trigger chest pain. Because a long-onset latency is associated with the bradykinin effect on cardiac spinal afferents, a cascade of intracellular signaling events is likely involved in the action of bradykinin on cardiac nociceptors. In this study, we determined the signal transduction mechanisms involved in bradykinin stimulation of cardiac nociceptors. Cardiac dorsal root ganglion (DRG) neurons in rats were labeled by intracardiac injection of a fluorescent tracer, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholate (DiI). Whole cell current-clamp recordings were performed in acutely isolated DRG neurons. In DiI-labeled DRG neurons, 1 microM bradykinin significantly increased the firing frequency and lowered the membrane potential. Iodoresiniferatoxin, a highly specific transient receptor potential vanilloid type 1 (TRPV1) antagonist, significantly reduced the excitatory effect of bradykinin. Furthermore, the stimulating effect of bradykinin on DiI-labeled DRG neurons was significantly attenuated by baicalein (a selective inhibitor of 12-lipoxygenase) or 2-aminoethyl diphenylborinate [an inositol 1,4,5-trisphosphate (IP(3)) antagonist]. In addition, the effect of bradykinin on cardiac DRG neurons was abolished after the neurons were treated with BAPTA-AM or thapsigargin (to deplete intracellular Ca(2+) stores) but not in the Ca(2+)-free extracellular solution. Collectively, these findings provide new evidence that 12-lipoxygenase products, IP(3), and TRPV1 channels contribute importantly to excitation of cardiac nociceptors by bradykinin. Activation of TRPV1 and the increase in the intracellular Ca(2+) are critically involved in activation/sensitization of cardiac nociceptors by bradykinin.
Zi-Zhen Wu; Hui-Lin Pan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-05-09
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  293     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-04     Completed Date:  2007-08-30     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R276-83     Citation Subset:  IM    
Department of Anesthesiology and Pain Medicine, Unit 110, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA.
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MeSH Terms
Arachidonate 12-Lipoxygenase / metabolism
Bradykinin / pharmacology*
Calcium / physiology*
Chelating Agents / pharmacology
Egtazic Acid / analogs & derivatives,  pharmacology
Enzyme Inhibitors / pharmacology
Extracellular Space / physiology
Flavanones / pharmacology
Ganglia, Spinal / cytology,  physiology
Heart / innervation*
Inositol 1,4,5-Trisphosphate / physiology
Intracellular Space / physiology
Membrane Potentials / drug effects
Neurons, Afferent / drug effects,  physiology*
Nociceptors / drug effects
Rats, Sprague-Dawley
TRPV Cation Channels / physiology*
Thapsigargin / pharmacology
Grant Support
Reg. No./Substance:
0/Chelating Agents; 0/Enzyme Inhibitors; 0/Flavanones; 0/TRPV Cation Channels; 0/Trpv1 protein, rat; 491-67-8/baicalein; 58-82-2/Bradykinin; 67-42-5/Egtazic Acid; 67526-95-8/Thapsigargin; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate; 85233-19-8/1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; EC 12-Lipoxygenase

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