Depression of primary afferent‐evoked responses by GR71251 in the isolated spinal cord of the neonatal rat

Guo, Jian-Zhong; Yoshioka, Koichi; Yanagisawa, Mitsuhiko; Hosoki, Rumiko; Hagan, R.M.; Otsuka, Masanori

doi:10.1111/j.1476-5381.1993.tb13933.x

Cited by 23 publications

(20 citation statements)

References 34 publications

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“…The depressant effects of GR71251 and RP67580 on the descending fibre-evoked slow depolarization of motoneurones are therefore probably due to their blocking actions on tachykinin NK1 receptors. The contributions of NK2 and NK3 tachykinin receptors to the tachykininergic slow EPSP may be negligible, because our previous studies have shown that both NK2 and NK3 agonists had little or no depolarizing actions on neonatal rat spinal motoneurones (Yanagisawa & Otsuka, 1990;Guo et at. 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore it is likely that the tachykinins responsible for the slow EPSP are mainly contained in serotonergic descending fibres. Guo et al (1993) and Hosoki et al (1994) examined the pharmacological profiles of GR71251 and RP67580 in the neonatal rat spinal cord and showed that they were specific tachykinin NK1 receptor antagonists. Furthermore, RP68651, the inactive enantiomer of RP67580, had no effect on the descending fibre-evoked slow VRP.…”

Section: Discussionmentioning

confidence: 99%

“…In the presence of the EAA receptor antagonists, ketanserin The remaining depolarizing response in the presence of D-APV, CNQX and ketanserin had a slow time course (1-2 min) and the size of the response became larger with increases in the frequency (up to 50 Hz), number of pulses (up to thirty pulses) and pulse width (up to 2 ms). In the experiments described below we used the stimulation parameters of twenty pulses of 2 ms duration at 10 or 50 Hz with 15 min intervals (except for intracellular recordings; see Methods), which gave stable responses for at least 4 h. A Effects of tachykinin antagonists on the descending fibre-evoked slow depolarization To test whether tachykinins contribute to the descending fibre-evoked slow VRP that remained under the action of EAA and 5-HT receptor antagonists, we examined the effects of a peptide tachykinin NK1 receptor antagonist, GR71251 (Ward, Ewan, Jordan, Ireland, Hagan & Brown, 1990;Guo, Yoshioka, Yanagisawa, Hosoki, Hagan & Otsuka, 1993) and a non-peptide tachykinin NK1 receptor antagonist, RP67580 (Garret et al 1991;Hosoki, Yanagisawa, Guo, Yoshioka, Maehara & Otsuka, 1994) Tachykininergic significantly depressed the descending fibre-evoked slow VRP (Fig.2). When the concentration of GR71251 was cumulatively increased, its depressant effect was evident at 0-3 /SM, and at 5 uM the antagonist depressed the slow VRP to 587 + 3-6% of the control response (n= 6, P < 0-01).…”

Section: Methods Preparationmentioning

confidence: 99%

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Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

Kurihara

Yoshioka

Otsuka

1995

The Journal of Physiology

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1. In the isolated spinal cord of the neonatal rat, repetitive electrical stimulation of the upper cervical region elicited a prolonged depolarization of lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly from ventral roots, or intracellularly. 2. This depolarizing response was markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (D-APV, 30 /M) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10/uM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 /LM).3. In the presence of these antagonists, a small part of the depolarizing response of slow time course remained, and this response was partially blocked by the tachykinin NK, receptor antagonists GR71251 (0 3-5 AM) and RP67580 (0 3-1 /SM). In contrast, RP68651(0 3-1 /sM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin wasmarkedly potentiated by a peptidase inhibitor, thiorphan (1 /SM).5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 #M), a neurotoxin for 5-HT neurones. Under such conditions, the effects of thiorphan and GR71251 on the slow depolarization were virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications of tachykinins, substance P and neurokinin A produced depolarizing responses of lumbar motoneurones, and the responses were depressed by GR71251 and potentiated by thiorphan. 7. These results suggest that tachykinins contained in serotonergic fibres serve as neurotransmitters mediating the descending fibre-evoked slow excitatory postsynaptic potentials in motoneurones.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methods Preparationmentioning

confidence: 99%

See 1 more Smart Citation

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

Kurihara

Yoshioka

Otsuka

1995

The Journal of Physiology

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“…When a lumbar (L3 ± 5) dorsal root was stimulated every 2 min with a single square pulse of 100 ms duration at 30 ± 40 V in an isolated spinal cord preparation, a monosynaptic re¯ex was elicited in the ipsilateral ventral root of the same segment and was followed by a slow VRP lasting about 30 s. Previous studies showed that the slow VRP was depressed by various tachykinin NK 1 receptor antagonists (Akagi et al, 1985;Guo et al, 1993), suggesting the involvement of SP and neurokinin A in the slow VRP. When monosynaptic re¯exes and slow VRPs became stable after about 1 h of perfusion with normal arti®cial CSF, wortmannin at 1 mM was added to the perfusion medium.…”

Section: Electrophysiological Experimentsmentioning

confidence: 99%

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat

Suzuki

Yoshioka

Maehara

et al. 1998

British J Pharmacology

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1 E ects of wortmannin, an inhibitor of myosin light chain kinase, on the release of substance P and amino acids, GABA and glutamate, were investigated in the isolated spinal cord preparation of the neonatal rat. 2 Wortmannin at 0.5 ± 10 mM depressed the release of substance P evoked by high-K + (90 mM) medium from the spinal cord (IC 50 =1.1 mM). Wortmannin also depressed the high-K + (70 mM)-evoked release of substance P from cultured dorsal root ganglion neurons of neonatal rats. In contrast, the high-K + (90 mM)-evoked release of GABA and glutamate from the spinal cord was not a ected by wortmannin (0.1 ± 10 mM). 3 Upon stimulation of a dorsal root, a monosynaptic re¯ex and a subsequent slow ventral root depolarization were evoked in the ipsilateral ventral root of the same segment in the isolated spinal cord preparation. The magnitude of the slow ventral root depolarization was depressed gradually to about 70% of the control during the course of 30 min under wortmannin (1 mM). In contrast, the monosynaptic re¯ex was una ected by wortmannin. 4 Immuno¯uorescent staining revealed that immunoreactivities of substance P and myosin II were colocalized at presynaptic terminals in the dorsal horn of the neonatal rat spinal cord. 5 The present results suggest that myosin phosphorylation by myosin light chain kinase may play a crucial role in the release of substance P, but not in the release of GABA and glutamate in the neonatal rat spinal cord. This may re¯ect a di erence in the exocytic mechanisms of substance Pcontaining large dense core vesicles and amino acid-containing small clear vesicles.

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“…This preparation enables us to obtain stable extracellular recording from ventral roots and thus to carry out detailed pharmacological analyses of both responses to nerve stimulation and responses to exogenously applied agents. Activation of primary afferent fibres by either electrical stimulation at C-fibre strength or peripheral noxious stimulation evokes a depolarization of a slow time course in ventral roots and this depolarization is markedly depressed by tachykinin antagonists as well as opioid agonists (Akagi et al, 1985;Otsuka & Yanagisawa, 1988;Nussbaumer et al, 1989;Yanagisawa et al, 1992;Guo et al, 1993;Hosoki et al, 1994). These and other lines of evidence suggest that this depolarization, hereafter referred to as the slow ventral root potential (VRP), represents a C-fibre-evoked nociceptive response in which tachykininergic primary afferents are involved (Otsuka & Yanagisawa, 1987).…”

Section: Introductionmentioning

confidence: 99%

The excitatory and inhibitory modulation of primary afferent fibre‐evoked responses of ventral roots in the neonatal rat spinal cord exerted by nitric oxide

Kurihara¹,

Yoshioka²

1996

British J Pharmacology

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1 We investigated the role of nitric oxide (NO) in modulating spinal synaptic responses evoked by electrical and noxious sensory stimuli in the neonatal rat spinal cord in vitro. 2 Potentials were recorded extracellularly from a ventral root (L3 -L5) of the isolated spinal cord preparation or spinal cord-saphenous nerve-skin preparation of 0-to 2-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or by noxious skin stimulation. 3 In the spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced mono-synaptic reflex followed by a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of NO gascontaining medium (l0-4-10-2 dilution of saturated medium) and NO donors, 1-hydroxy-2-oxo-3-(Nethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC12, 3-300 gM), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-300 gM) and S-nitroso-L-glutathione (GSNO, 3-300 gM), produced an inhibition of the slow VRP and a depolarization of ventral roots. Another NO donor, 3-morpholinosydononimine (SIN-1, 30-300 gM), also depressed the slow VRP but did not depolarize ventral roots. These agents did not affect the mono-synaptic reflex. 4 In the spinal cord-saphenous nerve-skin preparation, application of capsaicin (0.1-0.2 gM) to skin evoked a slow depolarizing response of the L3 ventral root. This slow VRP was depressed by NOC12 (10-300 gM) and SIN-I (100-300 gM). When the concentration of NOC12 was increased to 1 mM, spontaneous synaptic activities were augmented and the depressant effect of NOC12 on the slow VRP became less pronounced.5 A NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide(carboxy-PTIO, 100-300 pM) prevented the depressant effect on the dorsal root-evoked slow VRP and ventral root depolarizing effects of NO donors. Carboxy-PTIO increased spontaneous synaptic activities and markedly potentiated the slow VRP. A NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME, 0.03-1 uM), but not D-NAME (0.03-1 gM), also markedly potentiated the slow VRP and this effect was reversed by L-arginine (300 gM). 6 8-Bromo-cyclic guanosine 3': 5'-monophosphate (8-Br-cyclic GMP, 100-300 gM) produced both an inhibition of the slow VRP and a depolarization of ventral roots. A cyclic GMP-dependent protein kinase inhibitor, KT5823 (0.3 gM), partly inhibited the depressant effects of NO donors and 8-Br-cyclic GMP on the dorsal root-evoked slow VRP. In contrast, KT5823 did not inhibit the depolarizing effects of NO donors.7 Perfusion of the spinal cord with medium containing tetrodotoxin (0.3 gM) and/or low Ca21 (0.1 mM)-high Mg2e (10 mM) markedly potentiated the depolarizing effect of NO donors. The SNAPevoked depolarization in the tetrodotoxin-containing low Ca2+-high Mg2+ medium was significantly inhibited by excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (30 MM) and 6-cyano-7-nitroquinoxaline-...

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Depression of primary afferent‐evoked responses by GR71251 in the isolated spinal cord of the neonatal rat

Cited by 23 publications

References 34 publications

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat

The excitatory and inhibitory modulation of primary afferent fibre‐evoked responses of ventral roots in the neonatal rat spinal cord exerted by nitric oxide

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