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)

The functional interaction in the spinal cord between substance P and excitatory amino acid agonists was investigated. Behavioural responses were scored in mice after intrathecal administration of excitatory amino acid agonists and substance P, given separately or in combination. A strong potentiation of the effect was seen when substance P was coadministered with N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainic acid (KA). The potentiation was blocked by the corresponding antagonists: the selective NMDA-receptor antagonist (+/-)-3- (2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the substance P analog, [D-Arg1,D-Trp7,9,Leu11]-substance P (Spantide). These findings indicate a functional interaction between substance P and glutamate in the dorsal horn of the spinal cord, compatible with the hypothesis that corelease of substance P and glutamate from primary afferent neurons may enhance nociception.
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PMID:Potentiation of a behavioural response in mice by spinal coadministration of substance P and excitatory amino acid agonists. 172 10

Excitatory amino acid (EAA)-induced cell death in the striatum is dependent upon intact glutamatergic afferents arising from the cerebral cortex. Through a mechanism possibly related to inhibition of glutamate release, adenosine receptor agonists attenuate EAA induced toxicity in the rat striatum. In the present study, we examined whether 2-chloroadenosine (2CLA), a stable adenosine analog, protects against toxicity induced by kainate (KA), quisqualate (QUIS), N-methyl-D-aspartate (NMDA), and ibotenate (IBO). In vivo intrastriatal injections of 2CLA (50 nmol) with each EAA tested provided a partial but significant protective effect versus injection of the EAA alone, as measured by striatal concentrations of gamma-aminobutyric acid (GABA) and substance P-like immunoreactivity (SP-LI). These results show that 2CLA attenuates both NMDA- and non-NMDA-mediated neuronal cell death.
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PMID:2-Chloroadenosine attenuates NMDA, kainate, and quisqualate toxicity. 192 33

The effects of various neuroactive substances on the intracellular free Ca2+ concentration ([Ca2+]i) in cultured type-2 astrocytes were examined by fura-2-based microfluorometry. Type-2 astrocytes showed [Ca2+]i elevation in response to all the substances examined, i.e. carbachol (10(-4) M), histamine (10(-4) M), noradrenaline (10(-4) M), serotonin (10(-4) M), substance P (10(-6) M), vasopressin (10(-6) M) and glutamate (10(-4) M). Not all type-2 astrocytes, however, responded to these substances at the concentrations tested, and the percentages of astrocytes showing a Ca2+ response differed depending on the substance. These results indicate that type-2 astrocytes are potential targets for widely diverse neuroactive substances and heterogeneous in response to them.
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PMID:Type-2 astrocytes show intracellular Ca2+ elevation in response to various neuroactive substances. 194 45

In the present study we investigated the relative vulnerability of neuronal subsets in the striatum to ischemia that was induced by bilateral transient ligation of the common carotid arteries in gerbils. After 4 days of survival, brains were evaluated using histochemical methods (NADPH-diaphorase and silver degeneration procedures) and neurochemical methods with radioimmunoassays for somatostatin-, neuropeptide Y-, and substance P-like immunoreactivity and measurements of amino acids using high-pressure liquid chromatography with electrochemical detection. NADPH-diaphorase-positive neurons were strikingly preserved in the ischemic dorsolateral portion of the striatum, in which there was severe neuronal loss. There was no significant depletion of NADPH-diaphorase-positive neurons in the striatum or cerebral cortex. Concentrations of neuropeptide Y-like and somatostatin-like immunoreactivity were unchanged despite a significant 25% depletion of substance P-like immunoreactivity and gamma-aminobutyric acid. Ischemic brain damage may be mediated by a neurotoxic effect of glutamate acting at the N-methyl-D-aspartate (NMDA) receptor. Previous studies of NMDA excitotoxin lesions in rat striatum have shown a sparing of neurons containing NADPH-diaphorase, somatostatin, and neuropeptide Y. The similar sparing of these neurons following ischemic lesions in gerbil striatum provides further evidence that NMDA receptor activation may play a role in ischemic injury.
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PMID:Selective sparing of NADPH-diaphorase-somatostatin-neuropeptide Y neurons in ischemic gerbil striatum. 197 76

The last decade has seen tremendous progress in determining the nature of the neurotransmitters which regulate central nervous system pathways involved in the regulation of blood pressure. Investigations are now pursuing the identity and functional importance of neurotransmitters contained within pathways shown to be important in cardiovascular regulation. In addition, several key components of the brain stem networks involved in the control of sympathetic activity have been identified. For example, numerous studies indicate the importance of neurons located in the rostral ventrolateral medulla in the regulation of SPN. Indeed, this area contains medullospinal sympathoexcitatory neurons which represent the final site of integration of many brain stem and reflex pathways involved in the regulation of sympathetic nerve activity. The neurotransmitter which is utilized by this medullospinal pathway remains unknown. Epinephrine, substance P and glutamate have all been hypothesized as primary chemical mediators in the descending pathway from the brain stem to SPN. Interestingly, lesions of, or antagonists to, epinephrine, substance P, glutamate and 5-HT neurons all abolish sympathetic activity and reduce blood pressure to a level similar to that in a spinal animal. Clearly, not all these transmitters are primary mediators of sympathetic information carried from the brain stem to the spinal cord. It is likely that monoamines and neuropeptides act in the IML, as in other area of the central nervous system, as neuromodulators to set the level of excitability of SPN rather than relaying sympathetic information over a functionally specific medullospinal pathway. This conclusion is supported by the observation that midline medullary 5-HT neurons provide a tonic excitatory input to SPN, but receive no afferent inputs from other central sympathetic or baroreceptor pathways. However, the firing of 5-HT neurons appears to relate to the state of vigilance of the animal. This suggests that 5-HT neurons may lower the threshold of SPN to sympathetic inputs during states of wakefulness. In addition, the time course of the norepinephrine-mediated slow EPSPs and IPSPs in SPN is consistent with a gain-setting function. By analogy, epinephrine is likely to act as a neuromodulator in the IML rather than to serve as the primary mediator of sympathetic information descending from the rostral ventrolateral medulla.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of neurotransmitters in the central regulation of the cardiovascular system. 198 Dec 83

In order to determine which neurotransmitters and neuropeptides are utilized by the neurons of the mesencephalic trigeminal nucleus and by the fibres making synaptic contact with these primary sensory cells, we have set up an immunohistochemical study using antibodies against 17 major neurotransmitters and neuropeptides in the rat. Apart from some intracellular immunostaining for glutamate, no immunoreactivity to any of the tested neurotransmitters and neuropeptides could be detected inside mesencephalic nucleus of the trigeminal nerve neurons. Our immunohistochemical observations indicate that mesencephalic nucleus of the trigeminal nerve neurons receive input from various nerve fibres that appear to utilize serotonin, GABA, dopamine, noradrenaline (and likely glutamate) as transmitters. The innervation appeared randomly distributed over all mesencephalic nucleus of the trigeminal nerve neurons. The presence of substance P, cholecystokinin, vasoactive intestinal polypeptide, bombesin/gastrin releasing peptide, [Leu]enkephalin and neuropeptide Y observed in some fibres that contact with mesencephalic nucleus of the trigeminal nerve neurons, presumably reflect the co-existence of these peptides with one of the neurotransmitters.
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PMID:Neurotransmitters and neuropeptides within the mesencephalic trigeminal nucleus of the rat: an immunohistochemical analysis. 198 70

This paper reviews the role of central serotonin-containing neurons in the control of blood pressure. Central serotonin nerves have their cell bodies in the brainstem in a number of discrete collections, from where they ascend to ramify throughout the brain, descend to terminate in the spinal cord, or send shorter projections terminating in medulla, pons, and midbrain. Activation of one important ascending serotonin pathway innervating the preoptic region of the hypothalamus causes an increase in blood pressure. Activation of a bulbospinal serotonin projection descending from the ventrolateral medulla (the B3 cell group) to terminate in the intermediolateral cell column (IML) also evokes a pressor response. This pressor response is independent of that elicited by stimulation of the ventrolateral medulla in the adjacent but separate area containing the C1 adrenaline cell group. The pressor action appears to depend on increased release of serotonin, as detected by microdialysis in the area of the IML, and to be mediated by serotonin receptors of the 5HT1 subclass, probably located on sympathetic preganglionic neurons. It is possible that neuroactive excitatory amino acids, such as glutamate or aspartate, and neuropeptides such as substance P, also play a part in the pressor response evoked by stimulation of the ventrolateral medulla in the area of the lateral B3 serotonin cells. This descending serotonin pathway also appears important in mediating the hypotensive action of the antihypertensive drugs methyldopa and clonidine.
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PMID:Central serotonergic mechanisms in cardiovascular regulation. 228 47

Lumbar spinal motoneurons of urethane-anesthetized rats were driven at stable low firing rates by automatically cycled iontophoretic applications of glutamate or aspartate. The effects of iontophoretically applied serotonin, substance P or thyrotropin-releasing hormone (TRH) on glutamate or aspartate-evoked activity were then tested. All 3 substances were found to enhance both glutamate- and aspartate-induced excitation of the motoneurons. This enhancement of excitability was usually preceded by a brief period of inhibition at current onset. Although the effects of serotonin and substance P were qualitatively remarkably similar, TRH differed in that TRH occasionally inhibited motoneuron excitability without subsequent facilitation, and tachyphylaxis developed for the facilitatory effects of TRH. After TRH desensitization, serotonin could still enhance spinal motoneuron excitability.
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PMID:A comparison of the effects of serotonin, substance P and thyrotropin-releasing hormone on excitability of rat spinal motoneurons in vivo. 240 2

Cystometric recordings were performed in pentobarbitone anaesthetized rats and the effects of baclofen on urinary bladder function were evaluated as their influence on bladder hyperactivity induced by 1-dihydroxyphenylalanine (L-dopa) after peripheral decarboxylase inhibition. The bladder response was inhibited by intracerebroventricularly (i.c.v., 4th ventricle, 0.1 microgram) as well as by systemically administered (10 mg/kg i.v.) baclofen. Intravenous naloxone but not i.v. bicuculline i.c.v. substance P or i.c.v. glutamate antagonized the inhibitory actions of i.c.v. or/and i.v. baclofen. It is suggested that baclofen depresses the hyperactive bladder by a central action that is unrelated to bicuculline sensitive gamma aminobutyric acid mechanisms, substance P or glutamate neurotransmission but that is possibly related to interference with opioid mechanisms.
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PMID:Central effects of baclofen on the L-dopa induced hyperactive urinary bladder of the rat. 241 73

Iontophoretically applied serotonin (5HT), substance P (SP), thyrotropin releasing hormone (TRH) and proctolin all enhanced spinal motoneuron activity evoked by glutamate in urethane-anesthetized rats. 5HT and SP produced more consistent facilitation of excitability both within and between motoneurons than did TRH and proctolin which failed to facilitate several motoneurons. It is concluded that 5TH, SP, TRH and proctolin, which appear to co-exist in various combinations in ventral horn terminals near spinal motoneurons, have complimentary effects on motoneuron excitability.
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PMID:Serotonin and co-localized peptides: effects on spinal motoneuron excitability. 241 8


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