Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008031 (chest pain)
 17,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Role of TRPV1 and intracellular Ca2+ in excitation of cardiac sensory neurons by bradykinin. 1749 Nov 15

Bradykinin is one of metabolites produced during myocardial ischemia and infarction that can activate cardiac spinal (sympathetic) sensory neurons to cause chest pain. The aim of this study was 1) to characterize the responses of thoracic superficial and deeper spinal neurons in rats to intrapericardial administration of bradykinin as a noxious cardiac stimulus; 2) to compare neuronal responses to bradykinin alone and a mixture of algogenic chemicals (serotonin, prostaglandin E(2), histamine, adenosine and bradykinin) used in a previous study. Extracellular potentials of single neurons in the T(3) spinal cord were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer 0.2 ml solution of bradykinin (10(-5) M, 1 min). The results showed that 10/33 (30%) superficial and 80/165 (48%) deeper spinal neurons responded to intrapericardial bradykinin. All 10 superficial responsive neurons and 72/80 (90%) deeper neurons were excited; 7 (9%) neurons were inhibited; one neuron showed excitation-inhibition response pattern. Of 72 neurons excited by bradykinin, 35 and 47 neurons exhibited short- and long-lasting responses patterns, respectively. The proportions of response patterns and maximal excitatory responses to bradykinin were similar to effects obtained with a mixture of algogenic chemicals. However, the time to peak (28.3+/-3.1 s) and recovery time of long-lasting excitatory responses to bradykinin alone (125.2+/-8.9 s, n=47) were significantly shorter than the responses of neurons to the algogenic mixture (38.6+/-3.8 s and 187.5+/-18.5 s, n=49, P<0.05). In conclusion, bradykinin might play a key role in spinal processing for cardiac nociception, although other components released during ischemia might affect time characteristics of a subtype of thoracic spinal neurons receiving noxious cardiac input.
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PMID:Bradykinin is involved in the mediation of cardiac nociception during ischemia through upper thoracic spinal neurons. 1944 57