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)

Previous studies have described the presence of alternating activity induced in left and right ventral roots of the neonate rat in vitro brainstem-spinal cord preparation, following application of certain neuroactive substances to the bathing solution. The present findings show the presence of chemically induced, adult-like coordinated airstepping demonstrated by electromyographic recordings in the hindlimb-attached in vitro brainstem-spinal cord preparation. Analysis of muscular activity demonstrated alternation between antagonists of one limb and between agonists of different limbs, as well as a proximodistal delay in agonists active at different joints of the same limb. Neuroactive agents were applied independently to either the brainstem or spinal cord bath. The substances surveyed in the present studies included some of those used previously, as well as additional compounds: bicuculline and picrotoxin (gamma-aminobutyric acid-ergic antagonists), N-methyl-D-aspartic acid (excitatory amino acid agonist), substance P, acetylcholine, carbachol (cholinergic agonist), and serotonin. Application of these substances to the brainstem bath produced rhythmic airstepping. Application of dopamine, aspartate, glutamate, and N-methyl-D-aspartic acid to the spinal cord bath also produced rhythmic airstepping, while application of acetylcholine produced tonic, long-lasting co-contractions. These findings reveal the presence of several neurochemical systems in the central nervous system that can be activated at birth to induce coordinated airstepping in the neonate rat in vitro brainstem-spinal cord preparation.
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PMID:Control of locomotion in vitro: II. Chemical stimulation. 171 Aug 60

A role for sensitization of nociceptors in the generation of primary hyperalgesia is well documented. More recent work has begun to define a role of an increased excitability of neurons within the spinal cord in the generation of secondary hyperalgesia. The present study demonstrates increased responses of primate spinothalamic neurons following co-administration of N-methyl-D-aspartic acid (NMDA) and substance P (SP) by micro-iontophoresis. Wide dynamic range and high threshold STT neurons in laminae I-VI showed an increased frequency of discharges following application of NMDA which was characterized by a slow onset to peak discharge rate and a slow return to background levels of discharge. Combined application of NMDA with SP resulted in an enhancement of responses to NMDA that often long outlasted the administration of SP. This increase in response of the cells to NMDA was not produced by repeated application of NMDA alone or following combined application of NMDA with an SP analog. NMDA responses were reduced or prevented in all cases by co-application of an NMDA-receptor antagonist. Finally, long-lasting potentiation of NMDA responses by SP was paralleled by enhanced responses to mechanical stimulation of skin. It is proposed that a mechanism involving the combined synaptic release of excitatory amino acids and peptides leads to secondary hyperalgesia.
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PMID:Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of N-methyl-D-aspartic acid and substance P. 172 95

The purpose of this study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region (MLR) to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (5-30 sec) which were repeated for several minutes (1-40 min). Such activity was blocked by injections of GABA and the GABA agonist, muscimol. Locomotion was induced by injection of substance P (SP), which also produced short, repeated episodes of locomotion. The more potent excitatory amino acid agonist, n-methyl-d-aspartic acid (NMDA), however, did produce dose-dependent, long-lasting (20 sec-5 min) locomotor episodes which were repeated over prolonged periods at the higher concentrations used (2-24 min). Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were blocked by injections of the excitatory amino acid antagonist, aminophosphonovalerionic acid (APV) (1-10 mM). Preliminary evidence suggests that carbachol (10-50 mM), a cholinergic agonist, inhibits NMDA-induced increases in muscle tone and episodes of stepping. The effect of carbachol was blocked by the cholinergic antagonist, atropine.
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PMID:Posterior midbrain-induced locomotion. 197 Sep 47

These experiments examined the effects of intrathecally administered gamma-aminobutyric acid (GABA) agonists on the effects of intrathecally administered excitatory amino acid (EAA) agonists: N-methyl-D-aspartic acid (NMDA), quisqualic acid and kainic acid. We have found that muscimol, a GABAA receptor agonist, but not baclofen, a GABAB receptor agonist, dose-dependently inhibited caudally directed biting and scratching behavior induced by all three EAA agonists. This nonselective blockade of the expression of effects mediated by all three types of EAA receptor is in marked contrast to the selective blockade of NMDA effects seen previously in the case of mu opioids and phencyclidine receptor agonists. Inhibition by muscimol was blocked with the GABAA receptor antagonist, bicuculline. Decreased latency or hyperalgesia in the tail-flick test, found previously to be induced selectively by NMDA and blocked by an NMDA receptor antagonist, was similarly affected by muscimol but not baclofen, each given intrathecally. However, muscimol prolonged the tail-flick latency only after presentation of NMDA suggesting a possible antinociceptive effect of GABAA agonists in the presence of agonists at NMDA receptors. This study together with the preceding paper resolves GABA-mediated spinal antinociception into two components: a GABAA agonist selectively blocks nociception involving EAA receptors whereas a GABAB agonist selectively blocks substance P spinal activity (the preceding paper).
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PMID:Muscimol, gamma-aminobutyric acidA receptors and excitatory amino acids in the mouse spinal cord. 246 78

Effects of some possible neurotransmitters such as GABA, adrenergic drugs, and 5-HT and their antagonists on the motility of Angiostrongylus cantonensis were studied. Paralysis was caused by GABA, avermectin BIa (Av-BIa), piperazine and alpha-adrenergic agonists such as adrenaline, noradrenaline, phenylephrine, clonidine and methoxamine, but not by beta-adrenergic agonists such as isoproterenol. The paralysis by GABA or Av-BIa was antagonized by GABA antagonists such as picrotoxin and/or bicuculline with cholinergic agents such as N-methylcytisine (N-MC) or eserine. The paralysis elicited by alpha-adrenergic agonists was antagonized by alpha-adrenergic antagonists such as phentolamine and dibenamine, but not by beta-adrenergic antagonists such as propranolol. 5-HT affected the motility of A. cantonensis paralytically or spastically. The paralysis induced by 5-HT was antagonized by alpha-adrenergic antagonists such as phentolamine and dibenamine, while the contraction induced by this compound was further stimulated by N-MC, but antagonized by strychnine. Other agents such as glutamine, glycine, aspartic acid, taurine, and substance P showed little effect on the motility of A. Cantonensis. From these findings on the neuropharmacological properties of A. cantonensis, it is suggested that this worm is useful as an excellent nematodal model for the investigation of anthelminthics. In addition, this worm may also useful as one of screening models of drugs affecting the central nervous system in mammals.
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PMID:Studies on chemotherapy of parasitic helminths (VIII). Effects of some possible neurotransmitters on the motility of Angiostrongylus cantonensis. 612 26

Joint pain is a common symptom in various forms of arthritis. Unfortunately, the mechanisms involved in the pathogenesis of joint pain are not well understood, but probably include peripheral and central neural mechanisms. The sympathetic system appears to interact with sensory afferents under pathological conditions, and this may be mediated directly via receptors on sensory neurons, or indirectly via inflammatory mediators. Classical inflammatory mediators such as serotonin and bradykinin appear to activate some nociceptive afferents and serotonin may sensitise these afferents to non-noxious stimuli in an inflamed joint. A purely sensory function has traditionally been ascribed to sensory afferents, but unmyelinated C fibres have in addition a neurosecretory role and release peptides such as substance P which may contribute to inflammation. Lastly, central sensitisation in the spinal cord may play an important role in the pathogenesis of joint pain. Activation of N-Methyl-D-Aspartate (NMDA) receptors and the wind-up phenomenon may be involved in central sensitisation.
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PMID:Neural mechanisms of joint pain. 750 3

The antinociceptive effects of intrathecally administered 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a potent 5-HT receptor agonist, were studied in three behavioral tests in mice: the tail-flick test and the intrathecal substance P and N-methyl-D-aspartic acid (NMDA) assays. Intrathecal administration of 5-MeO-DMT (4.6-92 nmol/mouse) produced a significant prolongation of the tail-flick latency. This action was blocked by 5-HT3 and gamma-aminobutyric acidA (GABAA) receptor antagonists but not by 5-HT2, 5-HT1A, 5-HT1B or 5-HT1S receptor antagonists. Binding studies indicated that 5-MeO-DMT had very low affinity for 5-HT3 receptors. 5-MeO-DMT inhibited biting behavior while increasing scratching behavior induced by intrathecally administered substance P. The inhibition of biting behavior was antagonized by intrathecal co-administration of 5-HT1B and GABAA receptor antagonists while 5-HT1A, 5-HT1S, 5-HT2 and 5-HT3 receptor antagonists had no effect. 5-MeO-DMT-enhanced scratching behavior was inhibited by all the antagonists used except ketanserin and bicuculline, suggesting the involvement of 5-HT1A, 5-HT1B, 5-HT1S, 5-HT3 and GABAA receptors. NMDA-induced biting behavior was inhibited by 5-MeO-DMT pretreatment; this action was antagonized by 5-HT1B, 5-HT3 and GABAA receptor antagonists. The involvement of these receptors in 5-MeO-DMT action suggests that it may promote release of 5-HT (5-hydroxytryptamine, serotonin).
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PMID:Intrathecal 5-methoxy-N,N-dimethyltryptamine in mice modulates 5-HT1 and 5-HT3 receptors. 750 56

In order to shed some light on the neurotransmitters in the spinothalamic tract (STT), we examined, biochemically and immunohistochemically, the contents of various neurotransmitter candidates in the terminal field of the STT after cervical hemi-chordotomy (HC) and dorsal quadrant-chordotomy (dQC) in the rat. Substance P (SP), calcitonin gene-related peptide (CGRP), enkephalin, neuropeptide Y, neurotensin, oxytocin and dynorphin A were analyzed immunohistochemically. The contents of neuropeptides (SP, CGRP and cholecystokinin octapeptide) were measured by radioimmunoassay and those of amino acids (aspartic acid, glutamic acid, gamma-aminobutyric acid (GABA) and glycine) and noradrenaline were determined using high-performance liquid chromatography. Cervical hemi-chordotomy, but not dQC, caused significant decreases of the SP-like immunoreactivity in and SP content of the ventral thalamus on the ipsilateral side, compared with that on the contralateral side and of rats subjected to sham-operation. However, neither HC nor dQC resulted in any changes in the ventral thalamic contents of other putative neurotransmitters examined. These results suggest that, in rats, the STT contains SP and that SP-positive fibers run in the ventral half of the ascending spinal tract at the cervical level.
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PMID:Substance P is a possible neurotransmitter in the rat spinothalamic tract. 753 53

The modulatory effect of spinal serotonin (5-HT)1 receptors on nociception was studied in mice. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, putative 5-HT1A agonists, m-trifluoromethylphenyl-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-1a)quinoxaline (CGS 12066B), 5-HT1B agonists, and 5-carboxamidotryptamine (5-CT), a mixed 5-HT1A and 5HT1B agonist, were used. Intrathecal administration of 8-OH-DPAT, buspirone and 5-CT (1-12 nmol/mouse) significantly facilitated the tail-flick reflex, whereas TFMPP and CGS 12066B prolonged tail-flick latency. When administered i.t. after s.c. pretreatment (25 min) with morphine sulfate, 8-OH-DPAT, buspirone and 5-CT shifted the morphine sulfate dose-response curve 3- to 5-fold to the right. Spiperone, propranolol and pindolol (mixed 5-HT1A and 5-HT1B antagonists) effectively reversed both the tail-flick facilitation and the antagonistic effect on morphine sulfate-induced antinociception produced by 8-OH-DPAT and 5-CT. In addition, simultaneous i.t. administration of 8-OH-DPAT with substance P or N-methyl-D-aspartic acid decreased biting but increased scratching behavior, an effect which is also blocked by the 5-HT1 antagonists. These results confirm and extend other reports on the facilitory role of 5-HT1A receptor subtype on nociceptive responses and support the involvement of 5-HT1B receptor subtype in the antinociceptive action of serotonin.
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PMID:Differential roles of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor subtypes in modulating spinal nociceptive transmission in mice. 768 14

Pretreatment of isolated mast cells with analogs of neurotensin 8-13 (NT8-13), in which the amino acids Leu13 or Ile12 are replaced with an aspartic acid (Asp13-NT8-13 or Asp12-NT8-13), inhibits the secretion of histamine in response to NT. A 10 min pretreatment with either analog (10 microM) inhibited NT-induced histamine release by 90% (Asp13-NT8-13) or by 98% (Asp12-NT8-13). At concentrations that are inhibitory, Asp13-NT8-13 and Asp12-NT8-13 alone elicit very little release (< 5% at 10 microM). In the continued presence of the analogs, the inhibitory effect lasts for more than 45 min; removal of the analogs resulted in restoration of sensitivity to NT within 10 min. Pretreatment with analog Asp13-NT8-13 resulted in a 39% inhibition of stimulation by substance P and a 52% inhibition of stimulation by histamine-releasing peptide (HRP). In contrast, pretreatment with analog Asp12-NT8-13 gave no inhibition of release by SP or HRP. Neither analog inhibited histamine release in response to bradykinin (BK), NT1-12, compound 48/80 (48/80), the calcium ionophore A23187, or anti-IgE stimulation of passively sensitized mast cells. Although Asp12-NT8-13 and Asp13-NT8-13 differ slightly in regard to the peptides they inhibit, both probably act at a step early in the stimulus-secretion coupling sequence; most likely before the rise in the level of free intracellular calcium that has been shown to accompany secretion in mast cells. It is suggested that these analogs exert their inhibitory effect on NT by competing with NT for a binding site on the mast cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibitory effects of the neurotensin8-13 analogs Asp13-NT8-13 and Asp12-NT8-13 on mast cell secretion. 768 73


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