Expression of mRNA for four subtypes of the proteinase-activated receptor in rat dorsal root ganglia

Zhu, Wanjun; Yamanaka, Hiroki; Obata, Koichi; Dai, Yi; Kobayashi, Kimiko; Kozai, Toyoko; Tokunaga, Atsushi; Noguchi, Koichi

doi:10.1016/j.brainres.2005.02.018

Cited by 53 publications

(54 citation statements)

References 21 publications

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“…5B; n=12 for each genotype) displayed similar sensitivities to stimulus intensities required to elicit flinching, jumping, and vocalization (p>0.05 for each response). Even though PAR1 is expressed in sensory neurons (Vergnolle et al, 2003;Zhu et al, 2005), these data suggest that PAR1−/− animals do not show detectable differences in nociceptive thresholds for thermal stimulation or electrical shock.…”

Section: Nociceptive Responsesmentioning

confidence: 81%

Learning and memory deficits in mice lacking protease activated receptor-1

Almonte

Hamill

Chhatwal

et al. 2007

Neurobiology of Learning and Memory

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The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally-motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1−/− animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally-motivated learning.

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Section: Nociceptive Responsesmentioning

confidence: 81%

Learning and memory deficits in mice lacking protease activated receptor-1

Almonte

Hamill

Chhatwal

et al. 2007

Neurobiology of Learning and Memory

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show abstract

“…In addition to its well known role in the platelet aggregation cascade, thrombin has been implicated in degenerative as well as protective mechanisms in the CNS. It is of interest to note that PAR-1, one of the thrombin receptor subtypes, is expressed in a subset of small and medium diameter of primary sensory neurons, suggesting that a thrombin/PAR-1 pathway plays a possible role in the transmission of pain (Zhu et al, 2005). It has been reported that responses to thrombin were found to be blocked by the specific thrombin inhibitor hirudin, a hirudin-derived peptide, which reflects the thrombin-specific nature of the cloned receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, PAR-1 is present in the developing and mature CNS (Fang et al, 2003). Zhu et al (2005) reported that PAR-1 is expressed not only in a subset of large-diameter primary sensory neurons but also in a subset of small-and medium-diameter primary sensory neurons of the spinal cord, which play an important role in the transmission of pain. The thrombin inhibitor hirdin, which is isolated from leech (Hirudo medicinalis), was characterized as a specific thrombin inhibitor in the late 1950s (Markwardt, 1957).…”

Section: Introductionmentioning

confidence: 99%

Protease-Activated Receptor-1 and Platelet-Derived Growth Factor in Spinal Cord Neurons Are Implicated in Neuropathic Pain after Nerve Injury

Narita

Usui²,

Narita³

et al. 2005

J. Neurosci.

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Recently, it has been reported that both thrombin-sensitive protease-activated receptor 1 (PAR-1) and platelet-derived growth factor (PDGF) are present not only in platelets, but also in the CNS, which indicates that they have various physiological functions. In this study, we evaluated whether PAR-1/PDGF in the spinal cord could contribute to the development of a neuropathic pain-like state in mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were significantly suppressed by repeated intrathecal injection of hirudin, which is characterized as a specific and potent thrombin inhibitor. Furthermore, a single intrathecal injection of thrombin produced long-lasting hyperalgesia and allodynia, and these effects were also inhibited by hirudin in normal mice. In nerveligated mice, the increase in the binding of

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“…PAR2 agonists, such as mast cell tryptase, activate submucosal (28), myenteric neurons (13) and jejunal and colonic afferent nerves (17,32). Although PAR2 expression has been identified in DRG (39) and enteric neurons (9,28), there is no study examining PAR2 expression in vagal nodose ganglion neurons. Moreover, few studies have provided direct evidence that mast cell tryptase released after mast cell degranulation acts on PAR2 to induce mechanical hypersensitivity in primary sensory afferent nerves in the gastrointestinal tract (17,32).…”

mentioning

confidence: 99%

TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus

Gao

Peterson³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Yu S, Gao G, Peterson BZ, Ouyang A. TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol 297: G34 -G42, 2009. First published May 7, 2009 doi:10.1152/ajpgi.00068.2009.-Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. Mast cell tryptase via protease-activated receptor 2 (PAR2)-mediated pathways sensitizes sensory nerves and induces hyperalgesia. Transient receptor potential A1 (TRPA1) plays an important role in mechanosensory transduction and nociception. Here we tested the hypothesis that mast cell activation via a PAR2-dependent mechanism sensitizes TRPA1 to induce mechanical hypersensitivity in esophageal vagal C-fibers. The expression profiles of PAR2 and TRPA1 in vagal nodose ganglia were determined by immunostaining, Western blot, and RT-PCR. Extracellular recordings from esophageal nodose neurons were performed in ex vivo guinea pig esophageal-vagal preparations. Action potentials evoked by esophageal distention and chemical perfusion were compared. Both PAR2 and TRPA1 expressions were identified in vagal nodose neurons by immunostaining, Western blot, and RT-PCR. Ninety-one percent of TRPA1-positive neurons were of small and medium diameters, and 80% coexpressed PAR2. Esophageal mast cell activation significantly enhanced the response of nodose C-fibers to esophageal distension (mechanical hypersensitivity). This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activationinduced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus. visceral afferent; sensitization; nociception; protease-activated receptor 2; transient receptor potential A1 ABNORMAL ESOPHAGEAL SENSATIONS are generated from sensory afferent nerve endings in the wall of the esophagus and transmitted to the central nervous system by both spinal (27, 31) and vagal (7,25,30,38) pathways. Esophageal sensory afferent nerves usually are polymodal with their cell bodies situated in either dorsal root ganglion (DRG) or nodose/jugular ganglia (21). A subtype of these afferent nerves, nociceptive afferent, can innervate noxious mechanical, chemical, and thermal stimuli to induce nociception (31,36,37). Under certain conditions, such as tissue damage or inflammation, these processes could be enhanced by peripheral and/or central sensitization and result in esophageal hyperalgesia (14,...

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Expression of mRNA for four subtypes of the proteinase-activated receptor in rat dorsal root ganglia

Cited by 53 publications

References 21 publications

Learning and memory deficits in mice lacking protease activated receptor-1

Learning and memory deficits in mice lacking protease activated receptor-1

Protease-Activated Receptor-1 and Platelet-Derived Growth Factor in Spinal Cord Neurons Are Implicated in Neuropathic Pain after Nerve Injury

TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus

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