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Tomoshige Koga - One of the best experts on this subject based on the ideXlab platform.
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The nucleus raphe magnus suppresses vomiting, and the solitary nucleus and 5-HT are not involved in this suppression.
Autonomic neuroscience : basic & clinical, 2009Co-Authors: Yuka Hattori, Tomoshige Koga, E Nakamura, Chie Hamaguchi, Yukiko Urayama, Yuko Yamada, Hiroyuki FukudaAbstract:In previous paper, we reported that stimulation of the nucleus raphe magnus (stim-NRM) inhibits the induction of Retching by afferent vagal fibers (VAs). We performed the present study to identity the transmitter of inhibition and then the site. The following results were obtained in decerebrated and paralyzed dogs. 1) The induction of fictive Retching was suppressed by i.v. injection of 5-HT, and by 4th ventricular administration of 5-HT or a 5-HT3-receptor (R) agonist, 1-(m-chlorophenyl)-biguanade hydrochloride (m-CPBG). 2) Both forms of suppression were antagonized by i.v. injection of ondansetron, a 5-HT3-R antagonist. 3) Administration of the antagonist into the 4th ventricle did not affect the induction or its suppression by stim-NRM. These results suggest that the transmission from VAs to neurons in the nucleus solitarius (NTS) is suppressed by 5-HT via 5-HT3-R. However, these results also suggest that both the transmitter and receptor are not involved in the induction of Retching by VAs or in its suppression by the NRM. Next, we examined the site of suppression. Unitary firings of NTS neurons in response to pulse-train stimulation of VAs were not inhibited by NRM stimulation. Moreover, the firing of NTS neurons during the induction of Retching by vagal stimulation did not significantly decrease with the superimposition of stim-NRM, although the induction of Retching was completely suppressed. These results suggest that suppression of the induction of Retching by the descending inhibitory system of pain did not occur in the synapse between afferent vagal fibers and NTS neurons. The site of suppression is discussed.
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The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus.
Brain Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the left medulla oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm rostral to the obex to eliminate the emetic function of that half. Fictive Retching induced by vagal stimulation was still observed after each of 32 injections (0.5–5 μg in 1–30 μl) in the area ventrolateral to the solitary complex in six dogs. Retching was also observed for 30 min or more after all but 2 of 30 injections (0.5–1 μg in 0.5–1 μl) in the area dorsal to the retrofacial nucleus in 17 dogs. In contrast, Retching disappeared within 5–30 min after each of 20 injections (0.5–1 μg in 1 μl) in the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15 dogs. The threshold dose for abolition of the Retching response was examined in seven dogs and was about 0.1 ng in 1 μl. The maximum velocity of salivation occurred before the onset of Retching and significantly decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area adjacent to the scAMB, and that neurons in the site induce prodromal signs and Retching in a sequential manner.
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the tachykinin nk1 receptor antagonist gr205171 abolishes the Retching activity of neurons comprising the central pattern generator for vomiting in dogs
Neuroscience Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract Tachykinin NK1 receptor antagonists are known to act centrally and to have broad-spectrum antiemetic effects, but their precise site of action has not yet been defined. To identify this site, the effects of the NK1 receptor antagonist GR205171 on the activities of neurons comprising the central pattern generator (CPG) for vomiting were observed in decerebrate paralyzed dogs. A non-respiratory neuron in each of nine dogs was considered to be a CPG neuron based on its response to abdominal vagal stimulation, its location in the CPG area in the reticular formation dorsomedial to the retrofacial nucleus, its firing patterns in prodromal and Retching phases and its response to apomorphine. In response to vagal stimulation at 3–10 Hz, the firing of these neurons transiently increased at the onset of stimulation (fast component), gradually increased again (slow component), and finally developed into rhythmic bursts synchronous with Retching bursts of the phrenic and abdominal muscle nerves. GR205171 (25–50 μg/kg, i.v.) abolished the slow component and Retching bursts in the neurons, and the Retching activities of both nerves, but did not change the fast component. The responses of these neurons to repetitive pulse–train vagal stimulation exhibited a vigorous ‘wind-up’ and finally developed into Retching bursts. Both the ‘wind-up’ phenomenon and Retching bursts disappeared after the application of GR205171. These results suggest that the site of the antiemetic action of NK1 receptor antagonists is located in the CPG or in the pathway connecting the solitary nucleus to the CPG.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs
Brain Research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05–0.7 mg kg−1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml−1, 30 μl) into the 4th ventricle abolished Retching, with latencies in excess of 120 min. These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs.
Brain research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05-0.7 mg kg-1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml-1, 30 microliters) into the 4th ventricle abolished Retching, with latencies in excess of 120 min These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
Hiroyuki Fukuda - One of the best experts on this subject based on the ideXlab platform.
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The nucleus raphe magnus suppresses vomiting, and the solitary nucleus and 5-HT are not involved in this suppression.
Autonomic neuroscience : basic & clinical, 2009Co-Authors: Yuka Hattori, Tomoshige Koga, E Nakamura, Chie Hamaguchi, Yukiko Urayama, Yuko Yamada, Hiroyuki FukudaAbstract:In previous paper, we reported that stimulation of the nucleus raphe magnus (stim-NRM) inhibits the induction of Retching by afferent vagal fibers (VAs). We performed the present study to identity the transmitter of inhibition and then the site. The following results were obtained in decerebrated and paralyzed dogs. 1) The induction of fictive Retching was suppressed by i.v. injection of 5-HT, and by 4th ventricular administration of 5-HT or a 5-HT3-receptor (R) agonist, 1-(m-chlorophenyl)-biguanade hydrochloride (m-CPBG). 2) Both forms of suppression were antagonized by i.v. injection of ondansetron, a 5-HT3-R antagonist. 3) Administration of the antagonist into the 4th ventricle did not affect the induction or its suppression by stim-NRM. These results suggest that the transmission from VAs to neurons in the nucleus solitarius (NTS) is suppressed by 5-HT via 5-HT3-R. However, these results also suggest that both the transmitter and receptor are not involved in the induction of Retching by VAs or in its suppression by the NRM. Next, we examined the site of suppression. Unitary firings of NTS neurons in response to pulse-train stimulation of VAs were not inhibited by NRM stimulation. Moreover, the firing of NTS neurons during the induction of Retching by vagal stimulation did not significantly decrease with the superimposition of stim-NRM, although the induction of Retching was completely suppressed. These results suggest that suppression of the induction of Retching by the descending inhibitory system of pain did not occur in the synapse between afferent vagal fibers and NTS neurons. The site of suppression is discussed.
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The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus.
Brain Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the left medulla oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm rostral to the obex to eliminate the emetic function of that half. Fictive Retching induced by vagal stimulation was still observed after each of 32 injections (0.5–5 μg in 1–30 μl) in the area ventrolateral to the solitary complex in six dogs. Retching was also observed for 30 min or more after all but 2 of 30 injections (0.5–1 μg in 0.5–1 μl) in the area dorsal to the retrofacial nucleus in 17 dogs. In contrast, Retching disappeared within 5–30 min after each of 20 injections (0.5–1 μg in 1 μl) in the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15 dogs. The threshold dose for abolition of the Retching response was examined in seven dogs and was about 0.1 ng in 1 μl. The maximum velocity of salivation occurred before the onset of Retching and significantly decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area adjacent to the scAMB, and that neurons in the site induce prodromal signs and Retching in a sequential manner.
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the tachykinin nk1 receptor antagonist gr205171 abolishes the Retching activity of neurons comprising the central pattern generator for vomiting in dogs
Neuroscience Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract Tachykinin NK1 receptor antagonists are known to act centrally and to have broad-spectrum antiemetic effects, but their precise site of action has not yet been defined. To identify this site, the effects of the NK1 receptor antagonist GR205171 on the activities of neurons comprising the central pattern generator (CPG) for vomiting were observed in decerebrate paralyzed dogs. A non-respiratory neuron in each of nine dogs was considered to be a CPG neuron based on its response to abdominal vagal stimulation, its location in the CPG area in the reticular formation dorsomedial to the retrofacial nucleus, its firing patterns in prodromal and Retching phases and its response to apomorphine. In response to vagal stimulation at 3–10 Hz, the firing of these neurons transiently increased at the onset of stimulation (fast component), gradually increased again (slow component), and finally developed into rhythmic bursts synchronous with Retching bursts of the phrenic and abdominal muscle nerves. GR205171 (25–50 μg/kg, i.v.) abolished the slow component and Retching bursts in the neurons, and the Retching activities of both nerves, but did not change the fast component. The responses of these neurons to repetitive pulse–train vagal stimulation exhibited a vigorous ‘wind-up’ and finally developed into Retching bursts. Both the ‘wind-up’ phenomenon and Retching bursts disappeared after the application of GR205171. These results suggest that the site of the antiemetic action of NK1 receptor antagonists is located in the CPG or in the pathway connecting the solitary nucleus to the CPG.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs
Brain Research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05–0.7 mg kg−1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml−1, 30 μl) into the 4th ventricle abolished Retching, with latencies in excess of 120 min. These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs.
Brain research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05-0.7 mg kg-1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml-1, 30 microliters) into the 4th ventricle abolished Retching, with latencies in excess of 120 min These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
Yasuteru Shiroshita - One of the best experts on this subject based on the ideXlab platform.
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The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus.
Brain Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the left medulla oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm rostral to the obex to eliminate the emetic function of that half. Fictive Retching induced by vagal stimulation was still observed after each of 32 injections (0.5–5 μg in 1–30 μl) in the area ventrolateral to the solitary complex in six dogs. Retching was also observed for 30 min or more after all but 2 of 30 injections (0.5–1 μg in 0.5–1 μl) in the area dorsal to the retrofacial nucleus in 17 dogs. In contrast, Retching disappeared within 5–30 min after each of 20 injections (0.5–1 μg in 1 μl) in the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15 dogs. The threshold dose for abolition of the Retching response was examined in seven dogs and was about 0.1 ng in 1 μl. The maximum velocity of salivation occurred before the onset of Retching and significantly decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area adjacent to the scAMB, and that neurons in the site induce prodromal signs and Retching in a sequential manner.
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the tachykinin nk1 receptor antagonist gr205171 abolishes the Retching activity of neurons comprising the central pattern generator for vomiting in dogs
Neuroscience Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract Tachykinin NK1 receptor antagonists are known to act centrally and to have broad-spectrum antiemetic effects, but their precise site of action has not yet been defined. To identify this site, the effects of the NK1 receptor antagonist GR205171 on the activities of neurons comprising the central pattern generator (CPG) for vomiting were observed in decerebrate paralyzed dogs. A non-respiratory neuron in each of nine dogs was considered to be a CPG neuron based on its response to abdominal vagal stimulation, its location in the CPG area in the reticular formation dorsomedial to the retrofacial nucleus, its firing patterns in prodromal and Retching phases and its response to apomorphine. In response to vagal stimulation at 3–10 Hz, the firing of these neurons transiently increased at the onset of stimulation (fast component), gradually increased again (slow component), and finally developed into rhythmic bursts synchronous with Retching bursts of the phrenic and abdominal muscle nerves. GR205171 (25–50 μg/kg, i.v.) abolished the slow component and Retching bursts in the neurons, and the Retching activities of both nerves, but did not change the fast component. The responses of these neurons to repetitive pulse–train vagal stimulation exhibited a vigorous ‘wind-up’ and finally developed into Retching bursts. Both the ‘wind-up’ phenomenon and Retching bursts disappeared after the application of GR205171. These results suggest that the site of the antiemetic action of NK1 receptor antagonists is located in the CPG or in the pathway connecting the solitary nucleus to the CPG.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs
Brain Research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05–0.7 mg kg−1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml−1, 30 μl) into the 4th ventricle abolished Retching, with latencies in excess of 120 min. These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs.
Brain research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05-0.7 mg kg-1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml-1, 30 microliters) into the 4th ventricle abolished Retching, with latencies in excess of 120 min These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
N Furukawa - One of the best experts on this subject based on the ideXlab platform.
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The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus.
Brain Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the left medulla oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm rostral to the obex to eliminate the emetic function of that half. Fictive Retching induced by vagal stimulation was still observed after each of 32 injections (0.5–5 μg in 1–30 μl) in the area ventrolateral to the solitary complex in six dogs. Retching was also observed for 30 min or more after all but 2 of 30 injections (0.5–1 μg in 0.5–1 μl) in the area dorsal to the retrofacial nucleus in 17 dogs. In contrast, Retching disappeared within 5–30 min after each of 20 injections (0.5–1 μg in 1 μl) in the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15 dogs. The threshold dose for abolition of the Retching response was examined in seven dogs and was about 0.1 ng in 1 μl. The maximum velocity of salivation occurred before the onset of Retching and significantly decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area adjacent to the scAMB, and that neurons in the site induce prodromal signs and Retching in a sequential manner.
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the tachykinin nk1 receptor antagonist gr205171 abolishes the Retching activity of neurons comprising the central pattern generator for vomiting in dogs
Neuroscience Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract Tachykinin NK1 receptor antagonists are known to act centrally and to have broad-spectrum antiemetic effects, but their precise site of action has not yet been defined. To identify this site, the effects of the NK1 receptor antagonist GR205171 on the activities of neurons comprising the central pattern generator (CPG) for vomiting were observed in decerebrate paralyzed dogs. A non-respiratory neuron in each of nine dogs was considered to be a CPG neuron based on its response to abdominal vagal stimulation, its location in the CPG area in the reticular formation dorsomedial to the retrofacial nucleus, its firing patterns in prodromal and Retching phases and its response to apomorphine. In response to vagal stimulation at 3–10 Hz, the firing of these neurons transiently increased at the onset of stimulation (fast component), gradually increased again (slow component), and finally developed into rhythmic bursts synchronous with Retching bursts of the phrenic and abdominal muscle nerves. GR205171 (25–50 μg/kg, i.v.) abolished the slow component and Retching bursts in the neurons, and the Retching activities of both nerves, but did not change the fast component. The responses of these neurons to repetitive pulse–train vagal stimulation exhibited a vigorous ‘wind-up’ and finally developed into Retching bursts. Both the ‘wind-up’ phenomenon and Retching bursts disappeared after the application of GR205171. These results suggest that the site of the antiemetic action of NK1 receptor antagonists is located in the CPG or in the pathway connecting the solitary nucleus to the CPG.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs
Brain Research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05–0.7 mg kg−1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml−1, 30 μl) into the 4th ventricle abolished Retching, with latencies in excess of 120 min. These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
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The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced Retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs.
Brain research, 1998Co-Authors: Hiroyuki Fukuda, E Nakamura, Tomoshige Koga, N Furukawa, Yasuteru ShiroshitaAbstract:Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on Retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05-0.7 mg kg-1, i.v.) abolished Retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of Retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of Retching. Administration of GR205171 (1 mg ml-1, 30 microliters) into the 4th ventricle abolished Retching, with latencies in excess of 120 min These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
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Changes in extrahepatic biliary motilities with emesis in dogs
Journal of The Autonomic Nervous System, 1995Co-Authors: Rui-yao Qu, N Furukawa, Hiroyuki FukudaAbstract:Abstract To investigate changes in motility of the extrahepatic biliary system associated with emesis, we measured the volume of the gallbladder and flow resistance through the sphincter of Oddi, as well as antral and duodenal contractilities before and during Retching in decerebrate paralyzed dogs. Motilities of the gallbladder, sphincter of Oddi, duodenum and antrum were enhanced with most episodes of fictive Retching elicited by stimulation of the central part of the severed dorsal, as well as the ventral trunk of the thoracic vagus nerve. These enhanced motilities persisted until the end of Retching. Motilities of the sphincter of Oddi and duodenum were sometimes transiently depressed at the beginning of Retching. This depression in the sphincter continued for only 13 ± 1.0 s, while the gallbladder contraction continued for 65 ± 3.4 s. Motilities were rarely enhanced by vagal stimulation when Retching was not elicited. These changes in motilities were abolished by bilateral vagotomy. The serum gastrin level was increased just after 10 min after Retching only when the ventral vagal trunk remained intact, while the plasma cholecystokinin level was not changed with Retching. These results suggest that bile evacuation is interrupted with emesis despite contraction of the gallbladder during Retching, since the sphincter of Oddi also contracts simultaneously.
Emi Nakamura - One of the best experts on this subject based on the ideXlab platform.
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The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus.
Brain Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the left medulla oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm rostral to the obex to eliminate the emetic function of that half. Fictive Retching induced by vagal stimulation was still observed after each of 32 injections (0.5–5 μg in 1–30 μl) in the area ventrolateral to the solitary complex in six dogs. Retching was also observed for 30 min or more after all but 2 of 30 injections (0.5–1 μg in 0.5–1 μl) in the area dorsal to the retrofacial nucleus in 17 dogs. In contrast, Retching disappeared within 5–30 min after each of 20 injections (0.5–1 μg in 1 μl) in the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15 dogs. The threshold dose for abolition of the Retching response was examined in seven dogs and was about 0.1 ng in 1 μl. The maximum velocity of salivation occurred before the onset of Retching and significantly decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area adjacent to the scAMB, and that neurons in the site induce prodromal signs and Retching in a sequential manner.
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the tachykinin nk1 receptor antagonist gr205171 abolishes the Retching activity of neurons comprising the central pattern generator for vomiting in dogs
Neuroscience Research, 1999Co-Authors: Hiroyuki Fukuda, N Furukawa, Tomoshige Koga, Emi Nakamura, Yasuteru ShiroshitaAbstract:Abstract Tachykinin NK1 receptor antagonists are known to act centrally and to have broad-spectrum antiemetic effects, but their precise site of action has not yet been defined. To identify this site, the effects of the NK1 receptor antagonist GR205171 on the activities of neurons comprising the central pattern generator (CPG) for vomiting were observed in decerebrate paralyzed dogs. A non-respiratory neuron in each of nine dogs was considered to be a CPG neuron based on its response to abdominal vagal stimulation, its location in the CPG area in the reticular formation dorsomedial to the retrofacial nucleus, its firing patterns in prodromal and Retching phases and its response to apomorphine. In response to vagal stimulation at 3–10 Hz, the firing of these neurons transiently increased at the onset of stimulation (fast component), gradually increased again (slow component), and finally developed into rhythmic bursts synchronous with Retching bursts of the phrenic and abdominal muscle nerves. GR205171 (25–50 μg/kg, i.v.) abolished the slow component and Retching bursts in the neurons, and the Retching activities of both nerves, but did not change the fast component. The responses of these neurons to repetitive pulse–train vagal stimulation exhibited a vigorous ‘wind-up’ and finally developed into Retching bursts. Both the ‘wind-up’ phenomenon and Retching bursts disappeared after the application of GR205171. These results suggest that the site of the antiemetic action of NK1 receptor antagonists is located in the CPG or in the pathway connecting the solitary nucleus to the CPG.