Prevention of the excitatory actions of bradykinin by inhibition of PGI2 formation in nodose neurones of the guinea‐pig.

Weinreich, Daniel; Koschorke, G M; Undem, Bradley J.; Taylor, Gail

doi:10.1113/jphysiol.1995.sp020618

Cited by 38 publications

(33 citation statements)

References 35 publications

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“…In that study, our group postulated that the long sustaining effect may have involved a slow release of chemical mediators (e.g., PGE 2 or bradykinin) from various cells in the airway mucosa on action of cationic proteins, as discussed above. Although a possible involvement of endogenous autacoids cannot be completely ruled out in the present study because certain potent mediators (e.g., PGE 2 or PGI 2 ) may still be released from isolated neurons or from nonneuronal satellite cells present in the culture (25,39,49), other potential contributing factors should also be considered. For example, it is possible that the sustaining action of MBP is related to cascades of intracellular signaling events triggered by the cationic protein in these neurons (37).…”

Section: Discussionmentioning

confidence: 97%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Gu Q, Wiggers ME, Gleich GJ, Lee L-Y. Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins. Am J Physiol Lung Cell Mol Physiol 294: L544-L552, 2008. First published January 4, 2008 doi:10.1152/ajplung.00271.2007.-It has been shown that airway exposure to eosinophil-derived cationic proteins stimulated vagal pulmonary C fibers and markedly potentiated their responses to lung inflation in anesthetized rats (Lee LY, Gu Q, Gleich GJ, J Appl Physiol 91: 1318 -1326, 2001). However, whether the effects resulted from a direct action of these proteins on the sensory nerves was not known. The present study was therefore carried out to determine the effects of these proteins on isolated rat vagal pulmonary sensory neurons. Our results obtained from perforated whole cell patch-clamp recordings showed that pretreatment with eosinophil major basic protein (MBP; 2 M, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked ϳ10 min after MBP and lasted for Ͼ60 min; in current-clamp mode, MBP substantially increased the number of action potentials evoked by both capsaicin and electrical stimulation. Pretreatment with MBP did not significantly alter the input resistance of these sensory neurons. In addition, the sensitizing effect of MBP was completely abolished when its cationic charge was neutralized by mixing with a polyanion, such as low-molecular-weight heparin or poly-L-glutamic or poly-L-aspartic acid, before its delivery to the neurons. Moreover, a similar sensitizing effect was also generated by other eosinophil granule-derived proteins (e.g., eosinophil peroxidase). These results demonstrate a direct, charge-dependent, and long-lasting sensitizing effect of cationic proteins on pulmonary sensory neurons, which may contribute to the airway hyperresponsiveness associated with airway infiltration of eosinophils under pathophysiological conditions. major basic protein; eosinophil cationic protein; eosinophil peroxidase; airway inflammation; airway hypersensitivity ASTHMA IS CHARACTERIZED BY chronic airway inflammation associated with airway infiltration of various inflammatory cells, particularly the eosinophils (7). Activated eosinophils are known to secrete a number of cationic proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) (16). Previous studies have shown that intratracheal instillation of eosinophil-derived cationic proteins such as MBP induces bronchoconstriction and bronchial hyperresponsiveness in a number of animal species (9,17,21). Similar effects can also be induced by intratracheal administration of synthetic cationic proteins such as poly-Llysine (PLL) (10,24,46).Most of the sensory inputs arising from airways and lungs are conducted in vagus nerves and their branches. Cell bodies of these sensory nerves reside in two adjacent but distinct anatomic structures, the nodose and intracranial jugular ganglia. It is known that Ͼ75% of vagal bronchopulmonar...

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Section: Discussionmentioning

confidence: 97%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Relevant for the role of secondary prostanoids in bradykinin signaling, bradykinin selectively enhanced PGI 2 release from guinea pig nodose neurons (767). Bradykinin, through activation of B 2 but not B 1 receptors, released PGE 2 from cultured rat trigeminal neurons which was reduced by PLA 2 inhibition and COX blockade (315).…”

Section: Arachidonic Acid Derivatives In Bradykinin Receptor Signalingmentioning

confidence: 99%

“…Later it was shown that the slow AHP in vagal sensory neurons involved influx of Ca 2ϩ through N-type voltage-gated Ca 2ϩ channels followed by Ca 2ϩ -induced Ca 2ϩ release from endoplasmic reticulum via ryanodine channels and subsequent activation of Ca 2ϩ -activated K ϩ channels (113). In rabbit and guinea pig nodose ganglion neurons, bradykinin inhibited the slow AHP, and this effect was shown to be mediated by prostanoids, among them PGI 2 (736,767,769). The shortening of the AHP may be involved in the neuronal excitatory action of bradykinin, because AHP plays a role in controlling the response pattern of sensory neurons, and it is responsible for the slowing of the firing rate known as spike frequency adaptation (113,768).…”

Section: Other Targets Of Bradykinin Receptor Signalingmentioning

confidence: 99%

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

Pethő

Reeh

2012

Physiological Reviews

241

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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“…Bradykinin B 2 receptor stimulation evokes the release of arachidonic acid in afferent neurons (Burgess et al, 1989;Gammon et al, 1989;Allen et al, 1992) and depolarizes the membrane potential of vagal (Undem and Weinreich, 1993;Kajekar et al, 1999) and dorsal root ganglion (Burgess et al, 1989;McGuirk and Dolphin, 1992) neuron cell bodies. In addition, bradykinin inhibits a calcium-dependent potassium current responsible for an afterspike hyperpolarization in nodose ganglion neurons (Weinreich et al, 1995). These effects are likely to be mediated in part by arachidonic acid metabolites derived from phospholipids in neuronal membranes inasmuch as the effect on the afterspike-hyperpolarization in acutely isolated nodose neurons was abolished by the cyclooxygenase inhibitor, indomethacin (Weinreich et al, 1995) and the lipoxygenase inhibitor, norhydroguaiaretic acid inhibited bradykinininduced trains of action potentials in rat cultured dorsal root ganglion neurons (McGuirk and Dolphin, 1992).…”

mentioning

confidence: 99%

“…In addition, bradykinin inhibits a calcium-dependent potassium current responsible for an afterspike hyperpolarization in nodose ganglion neurons (Weinreich et al, 1995). These effects are likely to be mediated in part by arachidonic acid metabolites derived from phospholipids in neuronal membranes inasmuch as the effect on the afterspike-hyperpolarization in acutely isolated nodose neurons was abolished by the cyclooxygenase inhibitor, indomethacin (Weinreich et al, 1995) and the lipoxygenase inhibitor, norhydroguaiaretic acid inhibited bradykinininduced trains of action potentials in rat cultured dorsal root ganglion neurons (McGuirk and Dolphin, 1992).…”

mentioning

confidence: 99%

A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

Carr¹,

Kollárik²,

Meeker³

et al. 2002

J Pharmacol Exp Ther

116

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Using single-unit extracellular recording techniques, we have examined the role of the vanilloid receptor-1 (VR1 aka TRPV1) in bradykinin-induced activation of vagal afferent C-fiber receptive fields in guinea pig isolated airways. Of 17 airway C-fibers tested, 14 responded to bradykinin and capsaicin, 2 fibers responded to neither capsaicin nor bradykinin, and 1 fiber responded to capsaicin but not bradykinin. Thus, every bradykinin-responsive C-fiber was also responsive to capsaicin. Bradykinin (200 l of 0.3 M solution) evoked a burst of approximately 130 action potentials in C-fibers. In the presence of the TRPV1 antagonist capsazepine (10 M), bradykinin evoked 83 Ϯ 9% (n ϭ 6; P Ͻ 0.01) fewer action potentials. Similarly, the TRPV1 blocker, ruthenium red (10 M), inhibited the number of bradykinin-evoked action potentials by 75 Ϯ 10% (n ϭ 4; P Ͻ 0.05). In the presence of 5,8,11,14-eicosatetraynoic acid (10 M), an inhibitor of lipoxygenase and cyclooxygenase enzymes, the number of bradykinin-induced action potentials was reduced by 76 Ϯ 10% (n ϭ 6; P Ͻ 0.05). Similarly, a combination of the 12-lipoxygenase inhibitor, baicalein (10 M) and the 5-lipoxygenase inhibitor ZD2138 [6-[3-fluoro-5-[4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl])phenoxy-methyl]-1-methyl-2-quinolone] (10 M) caused significant inhibition of bradykinin-induced responses. Our data suggest a role for lipoxygenase products in bradykinin B 2 receptor-induced activation of TRPV1 in the peripheral terminals of afferent C-fibers within guinea pig trachea.The pharmacological activation of primary afferent neurons often involves the opening of ligand-gated ion channels such as 5-hydroxytryptamine 3 receptors, P2X purinoceptors, nicotinic acetylcholine receptors, and vanilloid receptor 1 (TRPV1), the first cloned capsaicin receptor (Wood and Docherty, 1997). Upon agonist binding to these channels, their ion pore opens, allowing the influx of cations, resulting in a membrane depolarization of sufficient magnitude to initiate action potentials. Bradykinin, an endogenous metabolite of the kallikrein-kinin system often associated with inflammation, also directly activates nociceptive-like afferent neurons, but does so via metabotropic G protein-coupled bradykinin B 2

show abstract

Prevention of the excitatory actions of bradykinin by inhibition of PGI2 formation in nodose neurones of the guinea‐pig.

Cited by 38 publications

References 35 publications

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

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

A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

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