Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Slow ventral root potentials (slow VRP's) recorded from 1- to 5-day-old rat spinal cords are implicated in nociception, but there is controversy over their origin and persistence in the adult. The present study investigated changes in the role of substance P and NMDA receptors in slow VRP generation during the postnatal period (1-21 days). Through 9 days, dorsal root stimulation elicits slow VRP's with typical peak amplitudes at 3-4 s, decay time constants of 18-20 s, and durations > 20 s. After 11 days, peak amplitude shortens to < 1 s, decay time constant 4-5 s, and duration < 10 s. At 1-6 days, slow VRP's are sensitive to the NMDA receptor antagonist APV and the substance P antagonists spantide and CP 96,345. After 11 days, APV sensitivity is retained, but spantide and ability of substance P to evoke a response are diminished. Abbreviated slow VRP's in post-11-day spinal cords appear to correspond to the early APV-sensitive component of long-duration slow VRP's in younger animals. Attempts to restore long-duration slow VRP's in 12- to 14-day-old rat cords by blocking various inhibitory mechanisms were not successful. The results suggest that a substance P response, some of which is mediated by NK1 receptors, is lost with maturation of the cord. Either a developmental role played by substance P changes with maturity, or the motor neurons of the isolated post-11-day cord lose the capacity to sustain large long-duration plateau potentials.
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PMID:Substance P and NMDA receptor-mediated slow potentials in neonatal rat spinal cord: age-related changes. 128 36

The present study examined the effects of intrathecal (i.t.) injection of calcitonin gene-related peptide (CGRP) on caudally directed biting and scratching induced by i.t. substance P (SP), bombesin (BBS), strychnine (STR), and kainic acid (KA). CGRP alone (5.25, 10.5 and 21 nmol) had no effect on these behaviors, but CGRP pretreatment produced a dose-related enhancement of behaviors induced by SP or BBS, but not by KA or STR. 2-Amino-5-phosphonovaleric acid (APV, 25 nmol), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, did not block the CGRP potentiation of SP and BBS induced behaviors. CGRP, however, failed to enhance scratching and biting induced by a SP analogue [pGlu5-Mephe8-MeGly9]SP(5-11) (Dime-C7) that is resistant to enzymatic degradation by SP endopeptidase. These findings demonstrate that CGRP potentiates SP induced behavioral responses via inhibition of neuropeptide degradation and that this mechanism may serve as a physiological mechanism of SP modulation.
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PMID:Calcitonin gene-related peptide enhances substance P-induced behaviors via metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation. 137 8

Substance P and glutamate actions have separately been implicated in the generation of nociceptive-related slow ventral root potentials (slow VRPs). We report that slow VRPs are dependent on both substance P and NMDA receptor-mediated neurotransmission. Slow VRPs of 10-40 s duration were evoked by electrically stimulating a lumbar dorsal root and recorded at the corresponding ipsilateral ventral root in spinal cords isolated from 1- to 5-day-old rats; the monosynaptic reflex was also recorded. The NMDA receptor antagonist APV (5-20 microM) and the substance P antagonist spantide (10-20 microM) both reversibly depressed the slow VRP without affecting the monosynaptic reflex; spantide and APV applied together nearly abolished the slow VRP. The quisqualate-kainate receptor antagonist CNQX (1-5 microM) reduced the monosynaptic reflex and an early component of the slow VRP. A slow VRP could be elicited by brief (0.1-1.0 s) focal applications of either substance P (2-20 microM) or NMDA (10 microM), and also by CGRP (2-20 microM). Substance P-evoked and NMDA-evoked responses were blocked by their respective antagonists spantide and APV. Each was also cross-sensitive to the other antagonist. Both excitatory amino acids, acting on an NMDA receptor, and substance P, acting on a tachykinin receptor, thus appear to be involved in generating this slow potential. Both NMDA and tachykinin receptors are necessary to generate a full response.
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PMID:Substance P and NMDA receptors mediate a slow nociceptive ventral root potential in neonatal rat spinal cord. 172 44

Previous anatomical studies demonstrated the presence of descending projections from the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla (MED) in the cat. The present experiments were designed to determine if a similar low threshold locomotion-inducing area is present in the rat medulla. In addition, the nature of the neurochemical control of this area of the brain was explored using localized injections of neurochemical agents in the decerebrate rat during locomotion on a treadmill. A region virtually identical to that reported in the cat was found to lead to controlled locomotion on a treadmill following stimulation at low amplitude currents (less than or equal to 60 microA). Injections of cholinergic agonists into the MED of the rat induced locomotion which could be blocked by injections of cholinergic antagonists. In addition, injections of GABA antagonists were found to induce stepping which could be blocked by injections of GABA or GABA agonists. Substance P (SP) also was found to induce walking following injection into the MED of the rat. Injections of an excitatory amino acid agonist (NMDA) also were found to induce locomotion in the rat. These effects were blocked by injections of an excitatory amino acid antagonist (APV). Since these results had not been reported for the cat MED, a short series of experiments revealed that the MED in the cat also responded to NMDA.
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PMID:Medioventral medulla-induced locomotion. 218 47

The participation of excitatory amino acid (EAA) receptors in the responses of deep dorsal horn neurons to repetitive stimulation of dorsal roots was investigated using a spinal slice preparation and current-clamp and voltage-clamp techniques. Using EAA receptor and substance P (SP) receptor antagonists and current-clamp, slow excitatory synaptic response evoked by 10-20 Hz stimulation consisted of two depolarizing components: an initial component lasting 1-5 s and a late-one of 1-3 min duration. The initial and late components of the slow excitatory postsynaptic currents (EPSCs) can also be distinguished on the basis of their voltage-dependence and sensitivity to Mg2+ ions, D-2-amino-5-phosphonovalerate (D-APV) and 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX). In the presence of Mg2+, the initial component of the slow EPSC increased with membrane hyperpolarization, whereas the late component decreased. In a zero-Mg2+ medium, the initial component was potentiated, but the late component was reduced, or unchanged. CNQX reduced the initial component. In a zero-Mg2+ solution, or at membrane potentials positive to -55 mV in 1 mM Mg2+, D-APV reduced or even abolished the initial component, whereas the late component was not modified by D-APV. We propose that slow excitatory synaptic response evoked in deep dorsal horn neurons by repetitive stimulation of primary afferents has two components, an initial transient component that requires activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and a late longer-lasting peptidergic component that has been already described (Brain Res., 290 (1984) 336-341.
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PMID:Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in the rat spinal dorsal horn in vitro. 257 67

Rats given an intrathecal injection of substance P (0.3-10 nmol) or any of the excitatory amino acid agonists, N-methyl-D-aspartate (NMDA, 1-10 nmol), kainate (1 and 3 nmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 0.3-3 nmol), showed biting or licking the hind paws, scratching with the hind paws (only after substance P) and vocalization (only after excitatory amino acid agonists). The intrathecal co-administration of the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol), inhibited behavioral responses to NMDA (10 nmol) and substance P (10 nmol) but not to kainate (3 nmol). Co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol), suppressed responses to kainate (3 nmol), AMPA (3 nmol) and substance P (10 nmol) but not to NMDA (10 nmol). Co-administration of the substance P antagonist, CP-96,345 (3 nmol), inhibited the behavioral responses to substance P (10 nmol), but not to NMDA (10 nmol), kainate (3 nmol) and AMPA (3 nmol). The results suggest that the aversive behavior induced by intrathecal NMDA and non-NMDA agonists is mediated by activation of the corresponding glutamate receptors, but not by NK-1 receptors, and that the behavioral action of intrathecal substance P is mediated not only by direct activation of NK-1 receptors but also indirectly by NMDA and non-NMDA receptors for glutamate.
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PMID:Pharmacological evidence for involvement of excitatory amino acids in aversive responses induced by intrathecal substance P in rats. 750 86

The rat given an intrathecal injection of capsaicin (0.3-10 nmol/rat) through a lumbar puncture showed biting or licking the tail and hind paws. The substance P antagonist, CP-96,345 (3 nmol/rat), co-administered intrathecally with capsaicin (10 nmol/rat), caused a significant inhibition of the behavioral responses to capsaicin (10 nmol/rat). When co-administered intrathecally with the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol/rat), the capsaicin (10 nmol/rat) -induced behavioral responses were significantly inhibited. A co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol/rat), resulted in a significant reduction of the behavioral responses produced by capsaicin (10 nmol/rat). Administration of the combination of two antagonists (CP-96,345 and either APV or CNQX, or APV and CNQX) more markedly inhibited the behavioral responses to capsaicin (10 nmol/rat) than when either antagonist was co-administered with capsaicin. The results suggest that aversive behaviors induced by intrathecal capsaicin are mediated not only by the activation of NK-1 receptors but also by that of NMDA and non-NMDA receptors.
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PMID:Involvement of substance P and excitatory amino acids in aversive behavior elicited by intrathecal capsaicin. 751 12

To determine the role of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal horn in the hyperalgesia induced by repeated cold stress (RCS), we examined the effects of intrathecal injections of antagonists to NK-1, NMDA and non-NMDA receptors on the nociceptive threshold of RCS rats for paw-pressure stimulation. Intrathecal injections of the NK-1 antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (CP-96,345, 0.3-3 nmol/rat), the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV, 1-10nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) suppressed RCS-induced hyperalgesia in a dose-dependent manner, without affecting the nociceptive threshold of normal rats. Combinations of any two of CP-96,345 (3 nmol/rat), APV (10 nmol/rat), and CNQX (10 nmol/rat) did not produce a larger inhibition than that produced by their single doses. The present results suggest that the enhancement of the substance P-NK-1 receptor system and glutamate-NMDA and non-NMDA receptor systems in the spinal dorsal horn is at least partly involved in the RCS-induced hyperalgesia.
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PMID:Effects of intrathecally injected glutamate and substance P antagonists on repeated cold stress-induced hyperalgesia in rats. 753 76

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 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 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 NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. 4. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 microM), 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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PMID:Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord. 756 17

To reveal possible involvement of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the production of inflammatory hyperalgesia, we examined the effects of intrathecal injections of antagonists at those receptors on the nociceptive threshold of inflammatory hyperalgesic rats in the paw-pressure test. Intrathecal injections of the NK-1 antagonist CP-96,345 (0.3-3 nmol/rat), the NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 1-10 nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) dose-dependently suppressed adjuvant- and carrageenin-induced hyperalgesia, without effect on the nociceptive threshold of non-inflamed paws. Furthermore, to estimate whether inflammatory hyperalgesia is accompanied with an alteration of the responsiveness to substance P and excitatory amino acids, we examined the effects of injections of complete Freund's adjuvant (intradermal) and carrageenin (subcutaneous) on the aversive responses to intrathecal substance P and excitatory amino acid agonists. Both injections significantly potentiated the aversive behaviors elicited by intrathecal injections of excitatory amino acid agonists, NMDA (1 nmol/rat), a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 1 nmol/rat) and kainate (1 nmol/rat), but not those by substance P. The present results suggest that the enhancement of synaptic transmission mediated by substance P and excitatory amino acids in the spinal dorsal horn is at least partly involved in the production of inflammatory hyperalgesia, and that such a hyperalgesia is accompanied with the enhanced responsiveness to excitatory amino acids through NMDA and non-NMDA receptors, but not with changes in responsiveness to substance P.
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PMID:Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats. 951


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