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)

It has been shown that substance P(SP), as well as its carboxy and amino terminal fragments, affects a wide range of behaviors. In order to test the CNS activity of these fragments, we measured their effects on passive avoidance learning and monoamine activity. Following one-trial passive avoidance training, mice were injected intraventricularly with either a carboxy or amino terminal SP fragment (SP-C or SP-N), SP itself or phosphate-buffered saline (PBS). SP-N enhanced avoidance retention, which was tested 24 h after training. In a second experiment, monoamine activity was measured one hour after intraventricular injection of SP, PBS or SP fragments. SP-C decreased both nigral 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) and, to a lesser extent, 3,4-dihydroxyphenylacetic acid/dopamine, while SP-N increased nigral 5-HIAA/5-HT. It was concluded that SP-N and SP-C can exert behavioral and neurochemical effects that may be independent of the parent SP molecule.
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PMID:The effect of substance P and its fragments on passive avoidance retention and brain monoamine activity. 242 83

The frequency of occurrence of the adrenergic, cholinergic, 5-hydroxytryptamine (5-HT)-, substance P (SP)-, methionine-enkephalin (met-Enk)- and somatostatin (SOM)-immunoreactive fibres innervating the smooth muscle of the large intestine in Hirschsprung and control children was compared. It was observed a higher frequency of catecholamine-fluorescence, acetylcholinesterase-positive and SOM-immunoreactive fibres in the muscularis externa and muscularis mucosa of the aganglionic segment in Hirschsprung gut as compared to that in the sigmoid colon and rectum in controls. In contrast, the frequency of SP-, met-Enk- and 5-HT-immunoreactive fibres in the aganglionic segment in Hirschsprung gut was lower than that in the controls. Ultrastructurally the cholinergic and adrenergic fibres occurred more often in the aganglionic segment in Hirschsprung gut than in the controls. A treatment with 6-OHDA and a fixation by Tranzer and Richards technique was used to confirm the nature of the adrenergic fibres. The p-type fibres occurred infrequently in the aganglionic segment of Hirschsprung gut. The results suggest that the change in the frequency of the nerves containing inhibitory transmitters may play an important role in the pathogenesis of Hirschsprung's disease.
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PMID:Histochemical, immunocytochemical and ultrastructural data on the innervation of the smooth muscle of the large intestine in Hirschsprung's disease. 242 97

The effects of bath perfusion of polyclonal and monoclonal antibodies to substance P (SP) on slow excitatory transmission in rat dorsal horn have been investigated by intracellular recording in the immature rat spinal cord slice preparation. Both polyclonal and monoclonal antibodies to SP produced a significant decrease in the amplitude and the duration of the slow depolarization generated in dorsal horn neurons by high intensity, repetitive dorsal root stimulation or exogenous SP application. The effect of endogenous SP, or SP-related peptide, released during dorsal root stimulation appears likely since bath perfusion of a slice with a normal rabbit serum, or affinity chromatography preadsorbed SP antiserum, or non-specific IgG, or 5-hydroxytryptamine antiserum had no similar depressant effect. These results, if taken together with other experimental evidence, suggest that SP, or SP-like peptide, is in some way involved in a generation of the dorsal root-evoked slow depolarization. In addition, a novel approach is presented for using polyclonal and monoclonal antibodies to SP as pharmacological antagonists. Use of a specific characterized monoclonal antibody for the detection of physiological and pharmacological effects of putative peptide transmitters in vitro opens new avenues for further investigations.
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PMID:Effects of polyclonal and monoclonal antibodies to substance P on slow excitatory transmission in rat spinal dorsal horn. 242 27

The distribution of substance P-, methionine-enkephalin-, somatostatin- and 5-hydroxytryptamine-immunoreactive nerve elements in Hirschsprung's disease was studied. It was compared to the distribution of the comparable nerve elements in the sigmoid colon and rectum of control children. A reduction of substance P-, methionine-enkephalin- and 5-hydroxytryptamine-immunoreactive fibers as well as a higher density of somatostatin-immunoreactive fibers were found in the aganglionic segment in Hirschsprung gut as compared to those in the ganglionic segment in Hirschsprung children and the large bowel in control children. The changes in the density of peptide- and 5-hydroxytryptamine-immunoreactive fibers suggest the participation of different transmitters or transmitter candidates in the pathogenesis of Hirschsprung's disease.
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PMID:Distribution of substance P-, methionine-enkephalin-, somatostatin- and serotonin-immunoreactive nerve elements of the large bowel in Hirschsprung's disease. 243 53

Neuromedin K and substance P (SP) enhanced the basal (5 mM K+) and potassium-evoked (40 mM K+) release of [3H]5-hydroxytryptamine ([3H]5-HT) from slices of the rat cerebral cortex. The effects of the two tachykinins were additive. The SP antagonist span-tide ([D-Arg1, D-Trp7.9, Leu11]-SP) (10(-6) M) inhibited the stimulatory effect of SP but not of neuromedin K on the release of [3H]5-HT. These findings suggest that the two tachykinins exhibit their effects on serotonin release at distinct receptor sites.
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PMID:Tachykinin regulation of serotonin release: enhancement of [3H]serotonin release from rat cerebral cortex by neuromedin K and substance P acting at distinct receptor sites. 243 95

The contribution of the myenteric plexus in the mechanical responses of rat jejunal longitudinal muscle produced by several enteric nerve substances was evaluated. The myenteric plexus of a segment of rat jejunum was destroyed by serosal application of benzalkonium chloride (BAC). Fifteen days after BAC treatment, both the BAC-treated and an orad control jejunal segment were removed and the mechanical responses of the longitudinal muscle produced by the following substances were examined: substance P, acetylcholine (ACh), 5-hydroxytryptamine (5-HT), cholecystokinin octapeptide (CCK-8), norepinephrine, vasoactive intestinal peptide (VIP), bombesin, [Leu5]enkephalin and somatostatin. Our results indicate that: substance P and norepinephrine produce their mechanical responses by acting predominantly on the longitudinal smooth muscle; 5-HT, CCK-8, ATP, VIP and neurotensin act predominantly through the myenteric plexus; ACh possesses both direct and indirect actions; and because the responses to [Leu5]enkephalin, bombesin and somatostatin were equivocal, a conclusion as to their site of action could not be made with this preparation.
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PMID:Differentiation between myenteric plexus and longitudinal muscle of the rat jejunum as the site of action of putative enteric neurotransmitters. 243 41

The distribution of thyrotrophin-releasing hormone (TRH), substance P, and the indoleamines [5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)] has been examined in selected regions of the thoracic and lumbar spinal cord of the rabbit using sensitive radioimmunoassays for the first two and HPLC with electrochemical detection for the indoleamines. The levels of TRH- and substance P-like immunoreactivity (TRH-I and SP-I, respectively) were greatest in the ventral and dorsal grey matter, respectively. The level of TRH-I in most thoracic regions was greater than that in equivalent lumbar regions, but the only segmental difference in SP-I was in the ventral grey matter, where the lumbar segment contained more immunoreactivity. 5-HT and 5-HIAA were more evenly distributed than either peptide and showed no segmental variation in levels in equivalent regions, but the ventral grey matter contained significantly higher levels of 5-HT and had a greater 5-HT/5-HIAA ratio than all other regions. The absolute levels and the overall distribution of SP-I, TRH-I, and indoleamines in the thoracolumbar cord of the rabbit was very similar to that previously reported in both rats and humans, and the possible functional role of the peptides and indoleamines in spinal neurones is discussed.
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PMID:Regional distribution of substance P- and thyrotrophin-releasing hormone-like immunoreactivity and indoleamines in the rabbit spinal cord. 243 14

The selective inhibitor of the reuptake of 5-hydroxytryptamine (5-HT), zimelidine, was administered intraperitoneally to mice (10 mg/kg) and nociceptive sensitivity was evaluated using the formalin test (20 microliters of 1% formalin, injected subcutaneously) and the assay for substance P (5 ng administered intrathecally). Zimelidine increased the behavioural response to formalin, but reduced the response to substance P. These effects of zimelidine seemed to be unchanged after chronic treatment (2 X 10 mg/kg for 14 days). It is suggested that zimelidine produces a central antinociceptive effect, but elicits a peripheral hyperalgesia, which predominates in the formalin test.
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PMID:Changes in nociception after acute and chronic administration of zimelidine: different effects in the formalin test and the substance P behavioural assay. 243 84

The effects of subchronic (14 day) treatment with the inhibitors at the uptake of monoamines, zimelidine, alaproclate and imipramine, on regional levels of substance P (SP) and other tachykinins in tissue in the central nervous system of the rat were studied by radioimmunoassay. In the ventral spinal cord, in which substance P is known to exist together with 5-hydroxytryptamine (5-HT), in the terminals of descending neurones, treatment with the selective inhibitors of the uptake of 5-HT zimelidine (2 X 10 mumol/kg p.o.) or alaproclate (2 X 10 mumol/kg or 2 X 20 mumol/kg p.o.), increased the level of substance P-like immunoreactivity (SP-LI). The effect of alaproclate appeared to be dose-dependent. After treatment with imipramine (2 X 10 mumol/kg p.o.) only a tendency to increased levels of substance P-like immunoreactivity spinal cord was seen. Treatment with alaproclate, at the highest dose level, also elevated the concentration of neurokinin A/neurokinin B-like immunoreactivity (NKA/NKB-LI) in the ventral spinal cord. In the frontal cortex, in which separate monoaminergic and tachykinin-containing neurones interact, treatment with imipramine reduced the levels of SP-LI and NKA/NKB-LI, while treatment with alaproclate had the opposite effect. In the periaqueductal grey matter, treatment with zimelidine and alaproclate increased the levels of SP-LI and NKA/NKB-LI, while treatment with imipramine increased only the level of NKA/NKB-LI. In conclusion, subchronic treatment of rats with inhibitors of the uptake of monoamines induced changes in levels of tachykinin in frontal cortex, periaqueductal grey and spinal cord. The selective inhibitors of the uptake zimelidine and alaproclate, had similar effects on levels of tachykinin, while the inhibitor of the uptake of 5-HT and noradrenaline, imipramine induced changes in the frontal cortex, which were qualitatively different from the effects of zimelidine and alaproclate. Furthermore, the levels of different tachykinins were not always changed in parallel by the same treatment.
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PMID:Effects of subchronic treatment with imipramine, zimelidine and alaproclate on regional tissue levels of substance P- and neurokinin A/neurokinin B-like immunoreactivity in the brain and spinal cord of the rat. 243 37

The cross influence of polypeptides (substance P, eledoisin) and neurotransmitters (acetylcholine, histamine, 5-hydroxytryptamine, ATP) on isolated guinea pig ileum involved a reduction or loss of muscle sensitivity. After the desensitization induced by one of the neurotransmitters the sensitivity of the ileum longitudinal muscle to polypeptides as estimated by the dissociation constant of the drug-receptor complex, decreased, i.e. a non-specific cross desensitization occurred. 5-hydroxytrpyptamine, however, increased the sensitivity to the polypeptides. A similar sensibilizing effect is characteristic of the polypeptides which, after application, increased 1.5-2.0-fold the height of the maximum muscle contraction and decreased 2-4-fold the dissociation constant. A possible involvement of polypeptides not only in their interaction with the target cells but also in the modulation of neurotransmitters, is discussed.
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PMID:[Reciprocal effect of polypeptides and mediators on the ileum of the guinea pig]. 244 Jul 34


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