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)

P-Chlorophenylalanine (PCPA) 250 mg/kg IP, was given to a group of rats. 72 hrs later the electro-acupuncture analgesia was tested and substance P (SP) in the brain stem and the lumbar spinal of the rats was determined by RIA. After PCPA injecting the electro-acupuncture no longer caused analgesia but lowered the pain threshold. Meanwhile the level of SP in the brain stem and lumbar spinal did not increased but much lowered than the group of vehicle injection combined with electro-acupuncture. It suggests that by PCPA depleting the 5-HT in CNS and abating the 5-HT-energic descending inhibition the electro-acupuncture no longer causes analgesia but promotes the SP transmitted release. It further suggests that in lower brain stem and spinal transmission of SP was regulated by descending inhibition. Analgesia of electro-acupuncture activates the 5-HT-energic descending inhibition and decreases the nociceptive transmission of SP partly.
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PMID:[The influence of P-chlorophenylalanine on the analgesia of electro-acupuncture and the level of SP in CNS of rats]. 170 62

The present work was carried out to observe the effect of intra-cerebroventricular (icv) injection of monoamine neurotransmitters, enkephalin and morphine on immunoreactive substance P(Ir-SP) contents in hypothalamus, striatum, hippocampus and pain threshold. The results were as follows: (1) After icv or intra-DR (dorsal raphe nucleus) injection of 5-HTP, the content of Ir-SP in hypothalamus significantly decreased and pain threshold markedly increased; After depletion of the 5-HT content in brain by pCPA or destruction of DR, the contents of Ir-SP were remarkably elevated in three brain regions by the former and in hypothalamus, striatum by the later. (2) The Ir-SP levels in the three brain regions and the pain threshold were not affected by the icv injection of NE, however, icv injection of DA caused a increase of Ir-SP concentration in striatum which was reversed by the DA receptor antagonist haloperidol, but without any change of the pain threshold. 7th day after icv injection of 6-OHDA, the content of Ir-SP in striatum significantly reduced. (3) Icv injection of met-enkephalin (MEK) or morphine could increase the Ir-SP levels in hypothalamus, striatum and the pain threshold, and above-mentioned effect of morphine could be prevented by the opioid receptor antagonist naloxone. Icv injection of leu-enkephalin (LEK) had no effects both on Ir-SP contents in three brain regions and the pain threshold.
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PMID:[Effect of monoamine neurotransmitters, enkephalin and morphine on substance P contents of several brain regions and pain threshold in rats]. 170 64

1. Intracellular recordings were made from neurones of the guinea-pig gall-bladder in vitro. Intracellular injection of horseradish peroxidase revealed a simple structure, consisting of a soma and a single process, but no discernible dendritic arborization. 2. The resting membrane potential was -50.5 +/- 0.4 mV and the input resistance was 80 M omega. 3. Gall-bladder neurones spiked only once at the onset of depolarizing current pulses. Action potentials were blocked by tetrodotoxin, but a Ca2(+)-dependent spike could be elicited in the presence of tetrodotoxin and tetraethylammonium. 4. Action potential after-hyperpolarizations had a duration of 172 +/- 3.7 ms and reversed at a membrane potential of -93 mV; this reversal potential was linearly related to the logarithm of the external potassium concentration. The initial phase of the after-hyperpolarization was inhibited by tetraethylammonium (1-10 mM) and was not affected by 3,4-diaminopyridine. The late phase of the after-hyperpolarization was blocked by apamin (10 nM) or curare (500 microM). Both the early and late phases of the after-hyperpolarization were inhibited when the preparation was perfused with a calcium-free, high-magnesium solution. The calcium-free, high-magnesium solution had no effect on the membrane potential or input resistance of these cells. 5. Fast excitatory synaptic responses and antidromic responses were elicited in gall-bladder neurones by focal stimulation of fibre tracts. High-frequency fibre tract stimulation often resulted in prolonged, calcium-dependent, depolarizations that were associated with a decrease in input resistance. 6. 5-Hydroxytryptamine and substance P caused depolarizations that were associated with a decrease in input resistance. Bethanechol caused hyperpolarizations that were associated with a decrease in input resistance and which were blocked by atropine.
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PMID:Intracellular recording from neurones of the guinea-pig gall-bladder. 170 71

The non-cholinergic late slow excitatory postsynaptic potential (ls-EPSP) of the guinea pig inferior mesenteric ganglion (IMG) was previously believed to be mediated by substance P (SP) or several other neuropeptides. Yet, the pharmacological evidence presented here indicates that serotonin (5-HT) may be another transmitter for the ls-EPSP in the guinea pig IMG. Repetitive stimulation of the presynaptic nerves elicited ls-EPSP in about half of the IMG neurons. Application of 5-HT or SP caused, in a portion of the IMG neurons, a slow depolarization similar to ls-EPSP. Fifty-six out of 88 (63.6%) neurons with ls-EPSP and 13 out of 35 (37.1%) neurons with ls-EPSP were sensitive to 5-HT and SP, respectively. Superfusion of the ganglia with 5-HT markedly suppressed the ls-EPSP evoked in 5-HT sensitive neurons. Similarly, exogenously applied SP attenuated the ls-EPSP of SP-sensitive neurons. However, prolonged superfusion of 5-HT or SP had no effect on the ls-EPSP elicited in 5-HT or SP-insensitive neurons, respectively. Furthermore, the ls-EPSPs elicited in 5-HT-sensitive neurons as well as the 5-HT-induced depolarization were reversibly suppressed by cyproheptadine, a 5-HT antagonist, and enhanced by fluoxetine, a 5-HT reuptake inhibitor. In contrast, the ls-EPSP of 5-HT insensitive neurons and SP-induced depolarization were not appreciably changed by those two drugs. Pretreatment with p-chlorophenylalanine, a 5-HT biosynthesis inhibitor, did not change the general electrophysiological characteristics of the neurons and did not suppress nicotinic neurotransmission, but markedly reduced the occurrence rate of ls-EPSP from 53.8% to 15.1% (P less than 0.005). Collectively, our results indicate that, besides SP, 5-HT may be involved in mediating the ls-EPSP in a subpopulation of neurons in the guinea pig IMG. The type of transmitter mediating ls-EPSP is apparently not limited to 5-HT and SP, as about 30% of the neurons with ls-EPSP were found to be insensitive to both 5-HT and SP and prolonged superfusion with both did not affect appreciably the ls-EPSP elicited in these neurons.
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PMID:The role of serotonin in non-cholinergic excitatory transmission in the guinea pig inferior mesenteric ganglion. 170 52

We studied smooth muscle strips from rabbit distal colon to determine age-related changes in length-tension properties and agonist-mediated contraction. Strips from newborn (1-d-old) and weanling (11-wk-old) rabbits were oriented to measure isometric tension in longitudinal muscle. Active tension comprised 47 +/- 4 and 75 +/- 5% of the total tension in the newborn and weanling, respectively. Total and active tensions in the weanling were greater than in the newborn (p less than 0.001). Although the potencies for bethanechol were similar, the maximal response was nearly 9-fold greater in weanlings (6900 +/- 292 mN/cm2) versus newborns (753 +/- 112 mN/cm2), p less than 0.001. Maximal stress increased with age for bethanechol, high extracellular potassium, substance P, neurokinin A, cholecystokinin octapeptide, bombesin, and serotonin. ED50 for bethanechol, substance P, neurokinin A, and bombesin did not change with age. Serotonin was 12 times more potent in newborns versus weanlings (p less than 0.05). In contrast, cholecystokinin octapeptide was five times less potent in newborns (18.6 nM versus 3.4 nM, respectively, p less than 0.05). Substance P-induced contractions were inhibited partially by atropine. We conclude that length-tension properties of longitudinal colonic smooth muscle differ, and responses to agonists increase with age.
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PMID:Developmental changes in agonist-mediated colonic smooth muscle contraction in the rabbit. 170 95

The autoradiographic distribution of the selective NK-3 tachykinin agonist [3H]senktide was investigated in rat brain. [3H]Senktide bound with high affinity (KD less than 2.5 nM) and high specificity (greater than 75%) to cerebral cortex and numerous subcortical sites, including the substantia nigra pars compacta. In addition, moderately dense binding was seen in the median but not the dorsal raphe nucleus, and this was disrupted by 5,7-dihydroxytryptamine (5,7-DHT)-induced destruction of 5-HT neurons. 5,7-DHT lesions did not affect the binding of [3H]senktide to forebrain regions, suggesting that 5-HT terminals are devoid of NK-3 receptors.
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PMID:Autoradiographic visualization of NK-3 tachykinin binding sites in the rat brain, utilizing [3H]senktide. 170 46

Extracellular levels of serotonin (5-hydroxytryptamine; 5-HT) were monitored by microdialysis in the dorsal vagal complex (DVC) and the ventral horn of the spinal cord at the level of the phrenic motor nucleus in decerebrated cats. A selective serotonin uptake inhibitor, alaproclate (10(-4) M) was included in the dialysis probe perfusion fluid to increase basal and stimulated levels of 5-HT. Electrical stimulation (30 Hz, 10 V, 0.5 ms) in the nucleus raphe obscurus, containing neurons projecting to the DVC and to the ventral horn, induced a 2-3-fold increase of the 5-HT release in both these regions. After termination of the stimulation, the release gradually decreased during the following 60 min. Substance P, which coexists with 5-HT in descending neurons, did not significantly affect the 5-HT release when it was added (100 microM) to the probe perfusion fluid. The present findings are in accordance with the hypothesis that prolonged release of 5-HT is responsible for the previously demonstrated long-lasting facilitation of phrenic activity following raphe obscurus stimulation.
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PMID:In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei. 170 56

Plasticity of spinal systems in response to lumbosacral deafferentation has previously been described for the cat, by using immunocytochemistry to demonstrate plasticity of tachykinin systems and degeneration methods to demonstrate plasticity of descending systems. In this study, we describe the response to lumbosacral deafferentation in the adult rat. Application of immunocytochemical methods to visualize tachykinins (predominantly substance P magnitude of SP), serotonin (5-HT), and dopamine B-hydroxylase (DBH), the synthesizing enzyme for norepinephrine, permits us to compare the response of SP systems in rat and cat spinal cord and to examine the response of two descending systems, serotoninergic and noradrenergic, to deafferentation. We used image analysis of light microscopic preparations to quantify the immunoreaction product in the spinal cord in order to estimate the magnitude, time course and localization of changes induced by the lesion. The distribution of SP, serotoninergic (5-HT), and noradrenergic staining in the spinal cord of rat is very similar to that of the cat. Unilateral lumbosacral rhizotomy elicits a partial depletion, followed by a partial replacement of tachykinin immunoreactivity in laminae I and II. This response was similar to that described for the cat, although characterized by a longer time course, and, as in the cat, is likely due to plasticity of tachykinin containing interneurons. The same lesion elicits no depletion but a marked and permanent increase in 5-HT immunoreactivity in laminae I and II, which develops more rapidly than the response by the SP system. These results indicate sprouting or increased production of SP and 5-HT in response to deafferentation. No change was seen in DBH immunoreactivity, indicating that the noradrenergic system does not show plasticity in response to deafferentation. Our results demonstrate that dorsal rhizotomy evokes different effects in different systems in the adult spinal cord of the rat and thus suggests that the response of undamaged pathways to partial denervation of their target is regulated rather than random.
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PMID:Plasticity of spinal systems after unilateral lumbosacral dorsal rhizotomy in the adult rat. 170 25

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
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PMID:Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 171 Jun 57

The influence of the serotonin (5-HT) system on the release of immunoreactive substance P after electrical stimulation of the lower incisor pulp was examined by perfusion of the superficial layers of the subnucleus caudalis of the brain stem trigeminal sensory nuclear complex of rabbits in situ. Increased release of immunoreactive substance P was observed after electrical stimulation of the pulp at 40 V. Stimulation of the nucleus raphe magnus significantly increased the release of 5-HT and completely inhibited the release of immunoreactive substance P, evoked by stimulation of the tooth pulp. Local application of 5-HT (10(-6) M) inhibited the release of immunoreactive substance P induced by stimulation and this inhibition was antagonized by methysergide (10(-4) M) applied concomitantly to the superficial layers of the trigeminal nucleus. These results suggest a functional interaction between substance P and 5-HT in the superficial layers of the trigeminal nucleus for regulation of transmission of dental pain.
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PMID:Serotonin inhibits release of substance P evoked by tooth pulp stimulation in trigeminal nucleus caudalis in rabbits. 171 Jul 94


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