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Naoki Yoshimura - One of the best experts on this subject based on the ideXlab platform.
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hyperexcitability of bladder Afferent Neurons associated with reduction of kv1 4 α subunit in rats with spinal cord injury
The Journal of Urology, 2013Co-Authors: William C De Groat, Ryosuke Takahashi, Tsuyoshi Yoshizawa, Takakazu Yunoki, Pradeep Tyagi, Seiji Naito, Naoki YoshimuraAbstract:Purpose: To clarify the functional and molecular mechanisms inducing hyperexcitability of C-fiber bladder Afferent pathways after spinal cord injury we examined changes in the electrophysiological properties of bladder Afferent Neurons, focusing especially on voltage-gated K channels.Materials and Methods: Freshly dissociated L6-S1 dorsal root ganglion Neurons were prepared from female spinal intact and spinal transected (T9-T10 transection) Sprague Dawley® rats. Whole cell patch clamp recordings were performed on individual bladder Afferent Neurons. Kv1.2 and Kv1.4 α-subunit expression levels were also evaluated by immunohistochemical and real-time polymerase chain reaction methods.Results: Capsaicin sensitive bladder Afferent Neurons from spinal transected rats showed increased cell excitability, as evidenced by lower spike activation thresholds and a tonic firing pattern. The peak density of transient A-type K+ currents in capsaicin sensitive bladder Afferent Neurons from spinal transected rats was sig...
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bladder hyperactivity and increased excitability of bladder Afferent Neurons associated with reduced expression of kv1 4 α subunit in rats with cystitis
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2009Co-Authors: Yukio Hayashi, William C De Groat, Michael B Chancellor, Koichi Takimoto, Krisrtin A Erickson, Vickie L Erickson, Tsukasa Kirimoto, Koushi Nakano, Naoki YoshimuraAbstract:Hyperexcitability of C-fiber bladder Afferent pathways has been proposed to contribute to urinary frequency and bladder pain in chronic bladder inflammation including interstitial cystitis. However, the detailed mechanisms inducing Afferent hyperexcitability after bladder inflammation are not fully understood. Thus, we investigated changes in the properties of bladder Afferent Neurons in rats with bladder inflammation induced by intravesical application of hydrochloric acid. Eight days after the treatment, bladder function and bladder sensation were analyzed using cystometry and an electrodiagnostic device of sensory function (Neurometer), respectively. Whole cell patch-clamp recordings and immunohistochemical staining were also performed in dissociated bladder Afferent Neurons identified by a retrograde tracing dye, Fast Blue, injected into the bladder wall. Cystitis rats showed urinary frequency that was inhibited by pretreatment with capsaicin and bladder hyperalgesia mediated by C-fibers. Capsaicin-sensitive bladder Afferent Neurons from sham rats exhibited high thresholds for spike activation and a phasic firing pattern, whereas those from cystitis rats showed lower thresholds for spike activation and a tonic firing pattern. Transient A-type K+ current density in capsaicin-sensitive bladder Afferent Neurons was significantly smaller in cystitis rats than in sham rats, although sustained delayed-rectifier K+ current density was not altered after cystitis. The expression of voltage-gated K+ Kv1.4 α-subunits, which can form A-type K+ channels, was reduced in bladder Afferent Neurons from cystitis rats. These data suggest that bladder inflammation increases bladder Afferent neuron excitability by decreasing expression of Kv1.4 α-subunits. Similar changes in capsaicin-sensitive C-fiber Afferent terminals may contribute to bladder hyperactivity and hyperalgesia due to acid-induced bladder inflammation.
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bladder overactivity and hyperexcitability of bladder Afferent Neurons after intrathecal delivery of nerve growth factor in rats
The Journal of Neuroscience, 2006Co-Authors: Naoki Yoshimura, William C De Groat, Nelson E Bennett, Yukio Hayashi, Teruyuki Ogawa, Osamu Nishizawa, Michael B Chancellor, Satoshi SekiAbstract:Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder Afferent Neurons. In adult female rats, NGF (2.5 μg/μl) was infused continuously into the intrathecal space at the L6–S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 μl/h). Bladder Afferent Neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6–S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder Afferent Neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder Afferent Neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder Afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder Afferent Neurons.
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Tetrodotoxin-resistant sodium channels Nav1.8/SNS and Nav1.9/NaN in Afferent Neurons innervating urinary bladder in control and spinal cord injured rats
Brain Research, 2003Co-Authors: Joel A. Black, William C De Groat, Naoki Yoshimura, Theodore R. Cummins, Stephen G. WaxmanAbstract:Abstract Tetrodotoxin-resistant (TTX-R) sodium channels Na v 1.8/SNS and Na v 1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) Neurons. The urinary bladder is innervated by small Afferent Neurons from L6/S1 DRG, of which ∼75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder Afferent Neurons. In the present study, we demonstrate that Na v 1.8 is expressed in both bladder and non-bladder Afferent Neurons, while Na v 1.9 is expressed in non-bladder Afferent Neurons but is rarely observed in bladder Afferent Neurons. In spinal cord transected rats 28–32 days following transection, there is a decreased expression of Na v 1.8 sodium channels in bladder Afferents, but no change in the expression of Na v 1.8 in non-bladder Afferent Neurons. Both bladder and non-bladder Afferent Neurons exhibit limited increases in Na v 1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder Afferent Neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these Neurons following spinal cord injury.
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Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in Afferent Neurons innervating urinary bladder in control and spinal cord injured rats.
Brain research, 2003Co-Authors: Joel A. Black, William C De Groat, Naoki Yoshimura, Theodore R. Cummins, Stephen G. WaxmanAbstract:Tetrodotoxin-resistant (TTX-R) sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) Neurons. The urinary bladder is innervated by small Afferent Neurons from L6/S1 DRG, of which approximately 75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder Afferent Neurons. In the present study, we demonstrate that Na(v)1.8 is expressed in both bladder and non-bladder Afferent Neurons, while Na(v)1.9 is expressed in non-bladder Afferent Neurons but is rarely observed in bladder Afferent Neurons. In spinal cord transected rats 28-32 days following transection, there is a decreased expression of Na(v)1.8 sodium channels in bladder Afferents, but no change in the expression of Na(v)1.8 in non-bladder Afferent Neurons. Both bladder and non-bladder Afferent Neurons exhibit limited increases in Na(v)1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder Afferent Neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these Neurons following spinal cord injury.
William C De Groat - One of the best experts on this subject based on the ideXlab platform.
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hyperexcitability of bladder Afferent Neurons associated with reduction of kv1 4 α subunit in rats with spinal cord injury
The Journal of Urology, 2013Co-Authors: William C De Groat, Ryosuke Takahashi, Tsuyoshi Yoshizawa, Takakazu Yunoki, Pradeep Tyagi, Seiji Naito, Naoki YoshimuraAbstract:Purpose: To clarify the functional and molecular mechanisms inducing hyperexcitability of C-fiber bladder Afferent pathways after spinal cord injury we examined changes in the electrophysiological properties of bladder Afferent Neurons, focusing especially on voltage-gated K channels.Materials and Methods: Freshly dissociated L6-S1 dorsal root ganglion Neurons were prepared from female spinal intact and spinal transected (T9-T10 transection) Sprague Dawley® rats. Whole cell patch clamp recordings were performed on individual bladder Afferent Neurons. Kv1.2 and Kv1.4 α-subunit expression levels were also evaluated by immunohistochemical and real-time polymerase chain reaction methods.Results: Capsaicin sensitive bladder Afferent Neurons from spinal transected rats showed increased cell excitability, as evidenced by lower spike activation thresholds and a tonic firing pattern. The peak density of transient A-type K+ currents in capsaicin sensitive bladder Afferent Neurons from spinal transected rats was sig...
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bladder hyperactivity and increased excitability of bladder Afferent Neurons associated with reduced expression of kv1 4 α subunit in rats with cystitis
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2009Co-Authors: Yukio Hayashi, William C De Groat, Michael B Chancellor, Koichi Takimoto, Krisrtin A Erickson, Vickie L Erickson, Tsukasa Kirimoto, Koushi Nakano, Naoki YoshimuraAbstract:Hyperexcitability of C-fiber bladder Afferent pathways has been proposed to contribute to urinary frequency and bladder pain in chronic bladder inflammation including interstitial cystitis. However, the detailed mechanisms inducing Afferent hyperexcitability after bladder inflammation are not fully understood. Thus, we investigated changes in the properties of bladder Afferent Neurons in rats with bladder inflammation induced by intravesical application of hydrochloric acid. Eight days after the treatment, bladder function and bladder sensation were analyzed using cystometry and an electrodiagnostic device of sensory function (Neurometer), respectively. Whole cell patch-clamp recordings and immunohistochemical staining were also performed in dissociated bladder Afferent Neurons identified by a retrograde tracing dye, Fast Blue, injected into the bladder wall. Cystitis rats showed urinary frequency that was inhibited by pretreatment with capsaicin and bladder hyperalgesia mediated by C-fibers. Capsaicin-sensitive bladder Afferent Neurons from sham rats exhibited high thresholds for spike activation and a phasic firing pattern, whereas those from cystitis rats showed lower thresholds for spike activation and a tonic firing pattern. Transient A-type K+ current density in capsaicin-sensitive bladder Afferent Neurons was significantly smaller in cystitis rats than in sham rats, although sustained delayed-rectifier K+ current density was not altered after cystitis. The expression of voltage-gated K+ Kv1.4 α-subunits, which can form A-type K+ channels, was reduced in bladder Afferent Neurons from cystitis rats. These data suggest that bladder inflammation increases bladder Afferent neuron excitability by decreasing expression of Kv1.4 α-subunits. Similar changes in capsaicin-sensitive C-fiber Afferent terminals may contribute to bladder hyperactivity and hyperalgesia due to acid-induced bladder inflammation.
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bladder overactivity and hyperexcitability of bladder Afferent Neurons after intrathecal delivery of nerve growth factor in rats
The Journal of Neuroscience, 2006Co-Authors: Naoki Yoshimura, William C De Groat, Nelson E Bennett, Yukio Hayashi, Teruyuki Ogawa, Osamu Nishizawa, Michael B Chancellor, Satoshi SekiAbstract:Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder Afferent Neurons. In adult female rats, NGF (2.5 μg/μl) was infused continuously into the intrathecal space at the L6–S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 μl/h). Bladder Afferent Neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6–S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder Afferent Neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder Afferent Neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder Afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder Afferent Neurons.
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Tetrodotoxin-resistant sodium channels Nav1.8/SNS and Nav1.9/NaN in Afferent Neurons innervating urinary bladder in control and spinal cord injured rats
Brain Research, 2003Co-Authors: Joel A. Black, William C De Groat, Naoki Yoshimura, Theodore R. Cummins, Stephen G. WaxmanAbstract:Abstract Tetrodotoxin-resistant (TTX-R) sodium channels Na v 1.8/SNS and Na v 1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) Neurons. The urinary bladder is innervated by small Afferent Neurons from L6/S1 DRG, of which ∼75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder Afferent Neurons. In the present study, we demonstrate that Na v 1.8 is expressed in both bladder and non-bladder Afferent Neurons, while Na v 1.9 is expressed in non-bladder Afferent Neurons but is rarely observed in bladder Afferent Neurons. In spinal cord transected rats 28–32 days following transection, there is a decreased expression of Na v 1.8 sodium channels in bladder Afferents, but no change in the expression of Na v 1.8 in non-bladder Afferent Neurons. Both bladder and non-bladder Afferent Neurons exhibit limited increases in Na v 1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder Afferent Neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these Neurons following spinal cord injury.
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Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in Afferent Neurons innervating urinary bladder in control and spinal cord injured rats.
Brain research, 2003Co-Authors: Joel A. Black, William C De Groat, Naoki Yoshimura, Theodore R. Cummins, Stephen G. WaxmanAbstract:Tetrodotoxin-resistant (TTX-R) sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) Neurons. The urinary bladder is innervated by small Afferent Neurons from L6/S1 DRG, of which approximately 75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder Afferent Neurons. In the present study, we demonstrate that Na(v)1.8 is expressed in both bladder and non-bladder Afferent Neurons, while Na(v)1.9 is expressed in non-bladder Afferent Neurons but is rarely observed in bladder Afferent Neurons. In spinal cord transected rats 28-32 days following transection, there is a decreased expression of Na(v)1.8 sodium channels in bladder Afferents, but no change in the expression of Na(v)1.8 in non-bladder Afferent Neurons. Both bladder and non-bladder Afferent Neurons exhibit limited increases in Na(v)1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder Afferent Neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these Neurons following spinal cord injury.
G J Dockray - One of the best experts on this subject based on the ideXlab platform.
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cocaine and amphetamine regulated transcript mediates the actions of cholecystokinin on rat vagal Afferent Neurons
Gastroenterology, 2010Co-Authors: Guillaume De Lartigue, R Dimaline, Andrea Varro, Helen E Raybould, Claire B De La Serre, G J DockrayAbstract:Background & Aims Cholecystokinin (CCK) acts on vagal Afferent Neurons to inhibit food intake and gastric emptying; it also increases expression of the neuropeptide cocaine- and amphetamine-regulated transcript (CART), but the significance of this is unknown. We investigated the role of CARTp in vagal Afferent Neurons. Methods Release of CART peptide (CARTp) from cultured vagal Afferent Neurons was determined by enzyme-linked immunosorbent assay. Expression of receptors and neuropeptides in rat vagal Afferent Neurons in response to CARTp was studied using immunohistochemistry and luciferase promoter reporter constructs. Effects of CARTp and CCK were studied on food intake. Results CCK stimulated CARTp release from cultured nodose Neurons. CARTp replicated the effect of CCK in stimulating expression of Y2R and of CART itself in these Neurons in vivo and in vitro, but not in inhibiting cannabinoid-1, melanin-concentrating hormone, and melanin-concentrating hormone-1 receptor expression. Effects of CCK on Y2R and CART expression were reduced by CART small interfering RNA or brefeldin A. Exposure of rats to CARTp increased the inhibitory action of CCK on food intake after short-, but not long-duration, fasting. Conclusions The actions of CCK in stimulating CART and Y2R expression in vagal Afferent Neurons and in inhibiting food intake are augmented by CARTp; CARTp is released by CCK from these Neurons, indicating that it acts as an autocrine excitatory mediator.
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cholecystokinin regulates expression of y2 receptors in vagal Afferent Neurons serving the stomach
The Journal of Neuroscience, 2008Co-Authors: G Burdyga, Guillaume De Lartigue, R Dimaline, Andrea Varro, Helen E Raybould, D G Thompson, R Morris, G J DockrayAbstract:The intestinal hormones CCK and PYY3–36 inhibit gastric emptying and food intake via vagal Afferent Neurons. Here we report that CCK regulates the expression of Y2R, at which PYY3–36 acts. In nodose ganglia from rats fasted up to 48 h, there was a fivefold decrease of Y2R mRNA compared with rats fed ad libitum ; Y2R mRNA in fasted rats was increased by administration of CCK, and by refeeding through a mechanism sensitive to the CCK1R antagonist lorglumide. Antibodies to Y2R revealed expression in both Neurons and satellite cells; most of the former (89 ± 4%) also expressed CCK1R. With fasting there was loss of Y2R immunoreactivity in CCK1R-expressing Neurons many of which projected to the stomach, but not in satellite cells or Neurons projecting to the ileum or proximal colon. Expression of a Y2R promoter-luciferase reporter (Y2R-luc) in cultured vagal Afferent Neurons was increased in response to CCK by 12.3 ± 0.1-fold and by phorbol ester (16.2 ± 0.4-fold); the response to both was abolished by the protein kinase C inhibitor Ro-32,0432. PYY3–36 stimulated CREB phosphorylation in rat nodose Neurons after priming with CCK; in wild-type mice PYY3–36 increased Fos labeling in brainstem Neurons but in mice null for CCK1R this response was abolished. Thus Y2R is expressed by functionally distinct subsets of nodose ganglion Neurons projecting to the stomach and ileum/colon; in the former expression is dependent on stimulation by CCK, and there is evidence that PYY3–36 effects on vagal Afferent Neurons are CCK dependent.
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cocaine and amphetamine regulated transcript stimulation of expression in rat vagal Afferent Neurons by cholecystokinin and suppression by ghrelin
The Journal of Neuroscience, 2007Co-Authors: Guillaume De Lartigue, R Dimaline, Andrea Varro, G J DockrayAbstract:The neuropeptide transmitter cocaine- and amphetamine-regulated transcript (CART) inhibits food intake and is expressed by both vagal Afferent and hypothalamic Neurons. Here we report that cholecystokinin (CCK) regulates CART expression in rat vagal Afferent Neurons. Thus, CART was virtually undetectable after energy restriction for 24 h, but administration of CCK to fasted rats increased CART immunoreactivity, and refeeding of fasted animals promptly increased CART by a mechanism sensitive to a CCK-1 receptor antagonist. In vagal Afferent Neurons incubated in serum-free medium, CART was virtually undetectable, whereas the orexigenic peptide melanin-concentrating hormone (MCH) was readily detected. The addition of CCK rapidly induced CART expression and downregulated MCH. Using a CART promoter–luciferase reporter vector transfected into cultured vagal Afferent Neurons, we showed that CCK stimulation of CART transcription was mediated by activation of protein kinase C and cAMP response element-binding protein (CREB). The action of CCK on CART expression was inhibited by the orexigenic peptide ghrelin, through a mechanism that involved exclusion of phosphorylated CREB from the nucleus. Thus, CCK reciprocally regulates expression of CART and MCH within the same vagal Afferent neuron; ghrelin inhibits the effect of CCK at least in part through control of the nuclear localization of phosphoCREB, revealing previously unsuspected modulation of gut–brain signals implicated in control of food intake.
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expression of cannabinoid cb1 receptors by vagal Afferent Neurons is inhibited by cholecystokinin
The Journal of Neuroscience, 2004Co-Authors: G Burdyga, R Dimaline, Andrea Varro, D G Thompson, G J DockrayAbstract:Both inhibitory (satiety) and stimulatory (orexigenic) factors from the gastrointestinal tract regulate food intake. In the case of the satiety hormone cholecystokinin (CCK), these effects are mediated via vagal Afferent Neurons. We now report that vagal Afferent Neurons expressing the CCK-1 receptor also express cannabinoid CB1 receptors. Retrograde tracing established that these Neurons project to the stomach and duodenum. The expression of CB1 receptors determined by RT-PCR, immunohistochemistry and in situ hybridization in rat nodose ganglia was increased by withdrawal of food for ≥12 hr. After refeeding of fasted rats there was a rapid loss of CB1 receptor expression identified by immunohistochemistry and in situ hybridization. These effects were blocked by administration of the CCK-1 receptor antagonist lorglumide and mimicked by administration of CCK to fasted rats. Because CCK is a satiety factor that acts via the vagus nerve and CB1 agonists stimulate food intake, the data suggest a new mechanism modulating the effect on food intake of satiety signals from the gastrointestinal tract.
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localization of orexin 1 receptors to vagal Afferent Neurons in the rat and humans
Gastroenterology, 2003Co-Authors: G Burdyga, R Dimaline, Andrea Varro, David G Spiller, Wen Jiang, D G Thompson, Stephen Attwood, Shakeel R Saeed, David Grundy, G J DockrayAbstract:Abstract Background & Aims: Orexin-A and -B are brain-gut peptides that stimulate food intake via orexin-R1 and -R2 receptors. Cholecystokinin (CCK) inhibits food intake via CCK A receptors expressed on vagal Afferent Neurons. The purpose of the study was to determine whether vagal Afferent Neurons express OX-R1 and OX-R2 and whether orexin-A inhibits responses to CCK. Methods: OX-R1 and -R2 expression by rat and human nodose ganglia was examined by reverse-transcriptase polymerase chain reaction (RT-PCR). Receptor localization was determined by immunohistochemistry. Responses of rat jejunal Afferent fibers were examined by electrophysiology. Results: Both rat and human nodose ganglia expressed OX-R1 as detected by RT-PCR, and humans also expressed OX-R2. The identity of the products was confirmed by sequencing. Immunohistochemistry indicated expression of OX-R1 in both species in Neurons that also expressed CCK A and leptin receptors. In human ganglia there was also expression in glial cells that was absent in rats. Orexin-A had no effect on the resting discharge of Afferent nerve fibers but inhibited responses to CCK. Conclusions: OX-R1 and CCK A receptors are expressed by human and rat vagal Afferent Neurons. Orexin inhibits responses to CCK suggesting a role in modulation of gut to brain signaling. GASTROENTEROLOGY 2003;124:129-139
Seog Bae Oh - One of the best experts on this subject based on the ideXlab platform.
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functional expression of thermo transient receptor potential channels in dental primary Afferent Neurons implication for tooth pain
Journal of Biological Chemistry, 2006Co-Authors: Chulkyu Park, Seyoung Choi, Kyungpyo Park, Zhi Fang, Hai Ying Li, Sung Jun Jung, Seog Bae OhAbstract:Abstract Temperature signaling can be initiated by members of transient receptor potential family (thermo-TRP) channels. Hot and cold substances applied to teeth usually elicit pain sensation. This study investigated the expression of thermo-TRP channels in dental primary Afferent Neurons of the rat identified by retrograde labeling with a fluorescent dye in maxillary molars. Single cell reverse transcription-PCR and immunohistochemistry revealed expression of TRPV1, TRPM8, and TRPA1 in subsets of such Neurons. Capsaicin (a TRPV1 agonist), menthol (a TRPM8 agonist), and icilin (a TRPM8 and TRPA1 agonist) increased intracellular calcium and evoked cationic currents in subsets of Neurons, as did the appropriate temperature changes (>43 °, <25 °, and <17 °C, respectively). Some Neurons expressed more than one TRP channel and responded to two or three corresponding stimuli (ligands or thermal stimuli). Immunohistochemistry and single cell reverse transcription-PCR following whole cell recordings provided direct evidence for the association between the responsiveness to thermo-TRP ligands and expression of thermo-TRP channels. The results suggest that activation of thermo-TRP channels expressed by dental Afferent Neurons contributes to tooth pain evoked by temperature stimuli. Accordingly, blockade of thermo-TRP channels will provide a novel therapeutic intervention for the treatment of tooth pain.
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eugenol inhibits calcium currents in dental Afferent Neurons
Journal of Dental Research, 2005Co-Authors: K Y Yeon, C K Park, H Y Li, Z Fang, Seyoung Choi, Kyungpyo Park, Seog Bae OhAbstract:Eugenol is a topical analgesic agent widely used in the dental clinic. To elucidate the molecular mechanism underlying its analgesic action, we investigated the effect of eugenol on high-voltage-activated calcium channel (HVACC) currents in dental primary Afferent Neurons, and with a heterologous expression system. Dental primary Afferent Neurons were identified by retrograde labeling with a fluorescent dye, DiI. Eugenol inhibited HVACC currents in both capsaicin-sensitive and capsaicin-insensitive dental primary Afferent Neurons. The HVACC inhibition by eugenol was not blocked by capsazepine, a competitive transient receptor potential vanilloid 1 (TRPV1) antagonist. Eugenol inhibited N-type calcium currents in the cell line C2D7, stably expressing the human N-type calcium channels, where TRPV1 was not endogenously expressed. Our results suggest that the HVACC inhibition by eugenol in dental primary Afferent Neurons, which is not mediated by TRPV1 activation, might contribute to eugenol’s analgesic effect...
Koichi Noguchi - One of the best experts on this subject based on the ideXlab platform.
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distinct expression of trpm8 trpa1 and trpv1 mrnas in rat primary Afferent Neurons with aδ c fibers and colocalization with trk receptors
The Journal of Comparative Neurology, 2005Co-Authors: Kimiko Kobayashi, Tetsuo Fukuoka, Atsushi Tokunaga, Hiroki Yamanaka, Koichi Obata, Koichi NoguchiAbstract:The transient receptor potential (TRP) superfamily of cation channels contains four temperature-sensitive channels, named TRPV1–4, that are activated by heat stimuli from warm to that in the noxious range. Recently, two other members of this superfamily, TRPA1 and TRPM8, have been cloned and characterized as possible candidates for cold transducers in primary Afferent Neurons. Using in situ hybridization histochemistry and immunohistochemistry, we characterized the precise distribution of TRPA1, TRPM8, and TRPV1 mRNAs in the rat dorsal root ganglion (DRG) and trigeminal ganglion (TG) Neurons. In the DRG, TRPM8 mRNA was not expressed in the TRPV1-expressing neuronal population, whereas TRPA1 mRNA was only seen in some Neurons in this population. Both A-fiber and C-fiber Neurons expressed TRPM8, whereas TRPV1 was almost exclusively seen in C-fiber Neurons. All TRPM8-expressing Neurons also expressed TrkA, whereas the expression of TRPV1 and TRPA1 was independent of TrkA expression. None of these three TRP channels were coexpressed with TrkB or TrkC. The TRPM8-expressing Neurons were more abundant in the TG compared with the DRG, especially in the mandibular nerve region innervating the tongue. Our data suggest heterogeneity of TRPM8 and TRPA1 expression by subpopulations of primary Afferent Neurons, which may result in the difference of cold-sensitive primary Afferent Neurons in sensitivity to chemicals such as menthol and capsaicin and nerve growth factor. J. Comp. Neurol. 493:596–606, 2005. © 2005 Wiley-Liss, Inc.
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phosphorylation of extracellular signal regulated kinase in primary Afferent Neurons by noxious stimuli and its involvement in peripheral sensitization
The Journal of Neuroscience, 2002Co-Authors: Koichi Iwata, Tetsuo Fukuoka, Eiji Kondo, Atsushi Tokunaga, Hiroki Yamanaka, Toshiya Tachibana, Koichi NoguchiAbstract:Alteration in the intracellular signal transduction pathway in primary Afferent Neurons may contribute to pain hypersensitivity. We demonstrated that very rapid phosphorylation of extracellular signal-regulated protein kinases (pERK) occurred in DRG Neurons that were taking part in the transmission of various noxious signals. The electrical stimulation of Aδ fibers induced pERK primarily in Neurons with myelinated fibers. c-Fiber activation by capsaicin injection induced pERK in small Neurons with unmyelinated fibers containing vanilloid receptor-1 (VR-1), suggesting that pERK labeling in DRG Neurons is modality specific. Electrical stimulation at the c-fiber level with different intensities and frequencies revealed that phosphorylation of ERK is dependent on the frequency. We examined the pERK in the DRG after application of natural noxious stimuli and found a stimulus intensity-dependent increase in labeled cell size and in the number of activated Neurons in the c- and Aδ-fiber population. Immunohistochemical double labeling with phosphorylated ERK/VR-1 and pharmacological study demonstrated that noxious heat stimulation induced pERK in primary Afferents in a VR-1-dependent manner. Capsaicin injection into the skin also increased pERK labeling significantly in peripheral fibers and terminals in the skin, which was prevented by a mitogen-activated protein kinase/ERK kinase inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminopheylthio)butadiene (U0126). Behavioral experiments showed that U0126 dose-dependently attenuated thermal hyperalgesia after capsaicin injection and suggested that the activation of ERK pathways in primary Afferent Neurons is involved in the sensitization of primary Afferent Neurons. Thus, pERK in primary Afferents by noxious stimulation in vivo showed distinct characteristics of expression and may be correlated with the functional activity of primary Afferent Neurons.
