Bradykinin decreases K<sup>+</sup> and increases Cl<sup>−</sup> conductances in vagal afferent neurones of the guinea pig

Oh, Eun Joo; Weinreich, Daniel

doi:10.1113/jphysiol.2004.066381

Cited by 46 publications

(42 citation statements)

References 34 publications

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“…Dorsal root and nodose ganglia were dissected from adult male rats (Sprague-Dawley, 200 -300 g) and dissociated as previously described (15). Acutely dissociated dorsal root ganglion (DRG) or nodose ganglion neurons, plated onto poly-D-lysine-coated No.…”

Section: Loading Of Dissociated Neurons With Fluorescent Ca 2+ Indicatormentioning

confidence: 99%

Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation

et al. 2006

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Nociceptive neurons in the peripheral nervous system detect noxious stimuli and report the information to the central nervous system. Most nociceptive neurons express the vanilloid receptor, TRPV1, a non-selective cation channel gated by vanilloid ligands such as capsaicin, the pungent essence of chili peppers. Here, we report the synthesis and biological application of two caged vanilloids-biologically inert precursors that, when photolyzed, release bioactive vanilloid ligands. The two caged vanilloids, Nb-VNA and Nv-VNA, are photoreleased with quantum efficiency of 0.13 and 0.041, respectively. Under flash photolysis conditions, photorelease of Nb-VNA and Nv-VNA is 95% complete in ∼40 μs and ∼125 μs, respectively. Through 1-photon excitation with ultraviolet light (360 nm), or 2-photon excitation with red light (720 nm), the caged vanilloids can be photoreleased in situ to activate TRPV1 receptors on nociceptive neurons. The consequent increase in intracellular free Ca 2+ concentration ([Ca 2+ ] i ) can be visualized by laser-scanning confocal imaging of neurons loaded with the fluorescent Ca 2+ indicator, fluo-3. Stimulation results from TRPV1 receptor activation, because the response is blocked by capsazepine, a selective TRPV1 antagonist. In Ca 2+ -free extracellular medium, photoreleased vanilloid can still elevate [Ca 2+ ] i , which suggests that TRPV1 receptors also reside on endomembranes in neurons and can mediate Ca 2+ release from intracellular stores. Notably, whole-cell voltage clamp measurements showed that flash photorelease of vanilloid can activate TRPV1 channels in < 4 msec at 22°C. In combination with 1-or 2-photon excitation, caged vanilloids are a powerful tool for probing morphologically distinct structures of nociceptive sensory neurons with high spatial and temporal precision. Keywords photolysis; photorelease; uncaging; molecular probes In the peripheral nervous system, nociceptive sensory neurons, or nociceptors, detect noxious stimuli and convert these stimuli into action potentials that are transmitted to the central nervous system (1). The vast majority of nociceptive neurons express the vanilloid receptor, TRPV1, 2 which is a ligand-gated non-selective cation channel with high permeability to

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Section: Loading Of Dissociated Neurons With Fluorescent Ca 2+ Indicatormentioning

confidence: 99%

Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation

et al. 2006

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“…In nodose ganglion neurons of the guinea pig, the B 2 receptor activation-induced membrane depolarization was reduced by the TRPV1 antagonist I-RTX, but an early component of the response was due to a decrease in resting K ϩ conductance followed by an increase in Ca 2ϩ -activated Cl Ϫ conductance (546). The latter mechanism, mediated by Ca 2ϩ -activated Cl Ϫ channels, can contribute to membrane depolarization, because primary afferent neurons have elevated intracellular Cl Ϫ concentrations owing to constitutive activity of the Na ϩ -K ϩ -2Cl Ϫ cotransporter that allows for an outflow of Cl Ϫ (580, 686).…”

Section: Other Targets Of Bradykinin Receptor Signalingmentioning

confidence: 99%

“…However, the complexity of the ion channel background of bradykinin's nociceptor-activating action is illustrated by a study on TRPV1-deficient mice, in which the nocifensive reaction evoked by a low dose of bradykinin applied intraplantarly was reduced compared with wild-type animals, but the effect of a higher dose was indistinguishable in the two genotypes of mice (337). It must be emphasized that in several studies the excitatory effects of bradykinin were not inhibited by either TRPV1 or TRPA1-selective antagonists, deletion of the TRPV1 or TRPA1 gene, or the broad-spectrum TRP channel inhibitor ruthenium red (20,67,151,161,232,309,337,356,374,436,546,591,611,791,792). These data indicate that non-TRP ion channels may also contribute to the excitatory/sensitizing effects of bradykinin (see sect.…”

Section: Trp Channels In Bradykinin Receptor Signalingmentioning

confidence: 99%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…Additional mechanisms for BK-induced hyperalgesia are mediated by PKCε (8), which in turn also causes TRPV1 sensitization (9). Unfortunately, the understanding of the molecular events underlying acute pain directly induced by BK is not that advanced and is mostly based on the electrophysiological observations of BK-induced depolarization (10,11), increased action potential (AP) firing (12), and inward current induction (10,12). BK has been referred to as "the most potent endogenous algogenic substance known" (2); thus, the elucidation of its modes and mechanisms of action should improve our ability to understand and treat spontaneous inflammatory pain.…”

Section: Introductionmentioning

confidence: 99%

The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl– channels

Liu¹,

Linley²,

Du³

et al. 2010

J. Clin. Invest.

263

442

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Bradykinin (BK) is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at sites of tissue damage or inflammation, or applied exogenously, BK produces acute spontaneous pain and causes hyperalgesia (increased sensitivity to potentially painful stimuli). The mechanisms underlying spontaneous pain induced by BK are poorly understood. Here we report that in small nociceptive neurons from rat dorsal root ganglia, BK, acting through its B 2 receptors, PLC, and release of calcium from intracellular stores, robustly inhibits M-type K + channels and opens Ca 2+ -activated Cl -channels (CaCCs) encoded by Tmem16a (also known as Ano1). Summation of these two effects accounted for the depolarization and increase in AP firing induced by BK in DRG neurons. Local injection of inhibitors of CaCC and specific M-channel openers both strongly attenuated the nociceptive effect of local injections of BK in rats. These results provide a framework for understanding spontaneous inflammatory pain and may suggest new drug targets for treatment of such pain.

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Bradykinin decreases K⁺ and increases Cl⁻ conductances in vagal afferent neurones of the guinea pig

Cited by 46 publications

References 34 publications

Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation

Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl– channels

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Bradykinin decreases K+ and increases Cl− conductances in vagal afferent neurones of the guinea pig

Cited by 46 publications

References 34 publications

Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation

Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl– channels

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Bradykinin decreases K⁺ and increases Cl⁻ conductances in vagal afferent neurones of the guinea pig