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 effect of resiniferatoxin on the isolated iris sphincter muscle of the rabbit was compared with the effects of capsaicin and bradykinin. The three compounds all contracted the sphincter muscle in a concentration-dependent manner. The contractions were inhibited by spantide II, a tachykinin antagonist. The concentration-response curve of resiniferatoxin was biphasic, yielding two EC50 values, one about 10,000 times lower than the other, the latter value being similar to that for capsaicin. The responses to resiniferatoxin, capsaicin or bradykinin were progressively reduced upon repeated application. The contraction evoked by either of the three compounds was not affected by thiorphan (an enkephalinase inhibitor) or captopril (an angiotensin-converting enzyme inhibitor). Pretreatment with capsaicin concentration dependently reduced the contractile response to a subsequent application of resiniferatoxin and vice versa. Bradykinin pretreatment reduced the resiniferatoxin response by about 50%; resiniferatoxin pretreatment completely abolished the response to bradykinin. Also, the contractile response to electrical stimulation was reduced concentration dependently by resiniferatoxin, capsaicin and bradykinin pretreatment. The response to electrical stimulation could be completely abolished by pretreatment with large doses of resiniferatoxin or capsaicin; pretreatment with large doses of bradykinin reduced the response by about 50%. Pretreatment with high concentrations of resiniferatoxin, or capsaicin, but not bradykinin, reduced the contractile response to the NK1 receptor agonist, [Sar9, Met(O2)11]SP (10(-8) M). The results suggest that the three compounds produce tachyphylaxis, mainly through partial (bradykinin) or complete (capsaicin, resiniferatoxin) exhaustion of the neuronal pool of releasable tachykinins although desensitization of tachykinin receptors may also contribute.
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PMID:Effect of resiniferatoxin on the isolated rabbit iris sphincter muscle: comparison with capsaicin and bradykinin. 138 78

In rats the parasympathetic auriculo-temporal nerve on one side was continuously stimulated at 40 Hz for 20-80 min in the presence of adrenergic blockers (dihydroergotamine and propranolol) +/- atropine. During the first 10 min this gave rise to a flow of saliva from the parotid gland that in the atropinized rats amounted to 35% of that found in rats not treated with atropine, while the protein and amylase outputs were 75% of those in non-atropinized rats. The atropine-resistant secretion of fluid and proteins declined to 5-10% of the initial value within 40 min but did not cease completely even after 80 min. The marked reduction in secretory responses was not due to desensitization or exhaustion of the gland cells. The nerve stimulation reduced the parotid gland content of vasoactive intestinal peptide (VIP) and substance P (SP) to approximately 60 and 25% of that of contralateral glands after 20 and 60 min, respectively. The probable explanation for the decline in secretory response seems to be depletion of non-adrenergic, non-cholinergic transmitter(s). The present results suggest that neuropeptides are involved in the regulation of salivary secretion but provide no direct evidence that either VIP or SP is responsible for the atropine-resistant salivary secretion.
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PMID:Depletion of neuropeptides in rat parotid glands and declining atropine-resistant salivary secretion upon continuous parasympathetic nerve stimulation. 241 6

This study was aimed at providing new knowledge on the pathology of Infantile Hypertrophic Pyloric Stenosis (IHPS) with some recently developed techniques and hence contributing to the understanding of its unsolved aetiology. Biopsy specimens of the pylorus were obtained from 15 children with IHPS at operation and 6 normal children at autopsy and compared as follows: (a) the presence or absence of muscle hyperplasia in IHPS was studied with special chromatin stain. No mitotic figures were observed in 10,000 cells screened; (b) Using the Schneider procedure, specimens from IHPS showed 1.47 +/- 0.09 mg DNA/g wet tissue (mean +/- SEM) compared with 2.38 +/- 0.18 mg DNA/g wet tissue in normal, defining the magnitude of muscular hypertrophy objectively to be in the region of 1.62 times normal; (c) Cholinesterase staining revealed adequate density of ganglia with no gross distortion of morphology in IHPS; (d) Immunocytochemical study with the marker neurone-specific-enolase confirmed that ganglia in IHPS were mature; (e) Immunocytochemical study with substance P revealed rich peptidergic innervation of the normal pylorus and a relative paucity in IHPS. This was interpreted as a phenomenon of exhaustion of substance P-neurones in IHPS. In conclusion, IHPS is a true muscle hypertrophy with little or no hyperplasia. The cholinergic ganglia are adequate and neural elements in general are sufficiently mature. The novel idea of possible disturbances of peptidergic innervation contributing to its aetiology has received some support.
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PMID:Observations and perspectives of the pathology and possible aetiology of infantile hypertrophic pyloric stenosis--a histological, biochemical, histochemical and immunocytochemical study. 241 61

Substance P (7.5-750 nM) applied in superfusion dose-dependently released 3H from isolated strips of myenteric plexus-longitudinal muscle of the guinea-pig ileum loaded with [3H]choline. Separation of the [3H]acetylcholine and [3H]choline components of the released radioactivity revealed that in response to substance P (SP) administration only the release of [3H]acetylcholine increased above resting level. A slowly developing tachyphylaxis to the effect of SP was observed. Evidence has been obtained that the slow tachyphylaxis developed to the acetylcholine-releasing effect of SP was not due to the exhaustion of releasable acetylcholine pool. Release of acetylcholine by 150 nM SP was completely prevented by tetrodotoxin or in a Ca2+-free medium and greatly reduced in the presence of noradrenaline or the opioid receptor agonist (D-Met2,Pro5)-enkephalinamide. The effect of noradrenaline and the opioid peptide was apparently prevented by yohimbine and naloxone, respectively.
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PMID:Presynaptic modulation by noradrenaline and an opioid of the substance P-induced release of [3H]acetylcholine from the myenteric plexus. 241 70

N-methyl-D-aspartate (NMDA) is an agonist used to identify neuronal receptive sites for dicarboxylic amino acid neurotransmitters; NMDA receptors are implicated in neuronal damage of ischemic or hypoglycemic origin in newborns although involved mechanisms remain to be identified. In the present study, 31P magnetic resonance spectroscopy with fast (6/min) data acquisition was used in newborn rat brain slices to measure changes of intracellular phosphocreatine and nucleotide triphosphate levels following extracellular NMDA applications. The rapid exhaustion of phosphocreatine stores in 50% of the total population of brain cells was induced in all cases by application of NMDA (30-45 s, 25-100 mM). It was not reproduced by other excitatory agents: potassium ions (24.6 mM, 4 min), isobutylxanthine (1mM), muscarine (10 mM), serotonin (0.1 mM) or substance P (10 microM). Such an effect of NMDA was not modified after tetrodotoxin (1 microM) and was reduced by extracellular 2-amino-5-phosphonovalerate (50 microM) or magnesium ions (2.2 mM). However it did develop during NMDA-induce neuronal excitations and was reversible within 10-30 min. This action of NMDA was followed by an irreversible decrease of phosphorus metabolites if mitochondrial creatine kinase and adenosine triphosphatase were decoupled by atractyloside (50 microM). Experiments revealed a link between selective NMDA action at neuronal plasma membranes, neurotoxicity and energy production by mitochondria.
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PMID:Metabolic action of N-methyl-D-aspartate in newborn rat brain ex vivo: 31p magnetic resonance spectroscopy. 268 43

INTRODUCTION--Cerebral blood vessels are innervated by sympathetic nerve fibres storing neuropeptide Y (NPY), parasympathetic nerves storing acetylcholine, vasoactive intestinal peptide (VIP) and sensory afferent fibres containing calcitonin gene-related peptide (CGRP), substance P (SP) and neurokinin A. In experimental studies on subarachnoid haemorrhage (SAH) there are indications that perivascular peptides are involved. In the present study we have in man measured the levels of NPY, VIP, SP and CGRP in brain vessels of patients that have suffered a fatal SAH and compared this with the levels encountered in subjects that died of an extracerebral cause. MATERIAL AND METHODS--Vessels from patients who have died from SAH or nonSAH were obtained during autopsy performed within 24 hrs after death. The peptides were extracted and fractionated with reversed phase liquid chromatography (HPLC). The levels of NPY, VIP, SP, and CGRP were measured with radioimmunoassay. Vasomotor responses of human cerebral arteries were performed using a sensitive in vitro system. RESULTS--Human cerebral vessels contained NPY, VIP, CGRP and SP which eluted at the same positions as the authentic peptides. The level of CGRP was significantly lower (p < 0.01) in arteries removed from SAH patients as compared to control subjects. The level of SP was not changed, if anything it tended to be increased after SAH. The levels of NPY and VIP were not significantly altered after SAH. In isolated brain vessels alpha-CGRP was a potent vasodilator of arteries precontracted with whole blood, prostaglandin F2 alpha or endothelin. It had a poor effect on vessels precontracted with 60 mM potassium. CONCLUSION--The evidence suggest that the trigemino-cerebrovascular system, storing CGRP and SP, is to a differential degree involved in the pathophysiology of SAH in man and supports the hypothesis of an exhaustion of CGRP as one important factor in the development of late spasm occurring after SAH.
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PMID:Perivascular neuropeptides (NPY, VIP, CGRP and SP) in human brain vessels after subarachnoid haemorrhage. 753 26

The purpose of our study was to clarify the role of capsaicin-sensitive nerves in the control of plasma catecholamine and glucose concentrations during exercise. In vehicle-treated rats, plasma epinephrine (E) and norepinephrine (NE) levels were significantly higher in animals exercised to exhaustion than in the group sacrificed at rest. However, it was not the case for the neonatally capsaicin-treated animals. The epinephrine and norepinephrine levels were not significantly higher in the capsaicinized animals exercised to exhaustion than in those studied at rest. As a result, plasma epinephrine and norepinephrine levels were higher in control than in capsaicinized exhausted animals. Impairment of capsaicin-sensitive nerves by the neonatal capsaicin treatment prevented the exercise-induced increase of catecholamine output despite a significant decrease in plasma glucose levels and a lower liver glycogen content at rest. We suggest that this impairment of catecholamine output during exercise was caused by depletion of substance P in C-fibers directed to the adrenal medulla. This is supported by the observation of a lower plasma epinephrine level in capsaicin-treated rats. We conclude that C-fibers are therefore involved in the control of catecholamine secretion by the adrenal medulla during exercise to exhaustion. However, such an impairment of catecholamine output was not associated with a further decrease in plasma glucose levels or a shorter time-to-exhaustion. This also suggests that a partial dysfunction of the adrenal medulla is not sufficient to alter exercise endurance and plasma glucose levels.
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PMID:Capsaicin-sensitive nerves and endurance exercise in the rat. 883 16

Intravenous injection of stearoyl vanillylamide (C18-VA), a nonpungent capsaicin (CAP) analog, enhances adrenaline secretion significantly and as effectively as CAP in rats. Because swimming capacity was enhanced by CAP in mice due to CAP-induced adrenal catecholamine secretion, we investigated the effects of oral administration of C18-VA on swimming capacity using an adjustable-current water pool. Male Std ddY 6-wk-old mice were fed a commercial diet for this study and one group was orally administered C18-VA via a stomach tube. Treated mice were able to swim longer before exhaustion than the control mice (62.9 +/- 5.6 vs. 49.6 +/- 7. 0 min, P < 0.05). The swimming capacity of two groups administered C18-VA (0.02 and 0.033 mmol/kg) was significantly greater than that of those administered vehicle alone, (P < 0.05). Substance P concentration in cerebrospinal fluid, which is involved in pain transmission and is the first direct measure of pungency, was not affected by C18-VA administration. In an experiment examining the effects of C18-VA on serum adrenaline concentration, adrenaline was significantly greater in C18-VA treated mice than in controls at 2-h post-dose (C18-VA group, 26.09 +/- 2.82; control group 13.29 +/- 0. 96 microg/L, P < 0.01). In a separate study free fatty acids in serum were elevated in treated mice at 2-h post-dose (P < 0.01). While serum glucose concentration was not affected. These results suggest that C18-VA increased swimming capacity of mice via adrenaline release, independent of pungency. In addition, the present study suggests the usefulness of its application to humans.
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PMID:Swimming capacity of mice is increased by oral administration of a nonpungent capsaicin analog, stearoyl vanillylamide. 980 52

Hematopoiesis is tightly regulated by the bone marrow (BM) niche. The niche is robust, allowing for the return of hematopoietic homeostasis after insults such as infection. Hematopoiesis is partly regulated by soluble factors, such as neuropeptides, substance P (SP), and neurokinin A (NK-A), which mediate hematopoietic stimulation and inhibition, respectively. SP and NK-A are derived from the Tac1 gene that is alternately spliced into four variants. The hematopoietic effects of SP and NK-A are mostly mediated via BM stroma. Array analyses with 2400 genes indicated distinct changes in SP-stimulated BM stroma. Computational analyses indicated networks of genes with hematopoietic regulation. Included among these networks is the high-mobility group box 1 gene (HMGB1), a nonhistone chromatin-associated protein. Validation studies indicated that NK-A could reverse SP-mediated HMGB1 decrease. Long-term culture-initiating cell assay, with or without NK-A receptor antagonist (NK2), showed a suppressive effect of HMGB1 on hematopoietic progenitors and increase in long-term culture-initiating cell assay cells (primitive hematopoietic cells). These effects occurred partly through NK-A. NSG mice with human hematopoietic system injected with the HMGB1 antagonist glycyrrhizin verified the in vitro effects of HMGB1. Although the effects on myeloid lineage were suppressed, the results suggested a more complex effect on the lymphoid lineage. Clonogenic assay for CFU- granulocyte-monocyte suggested that HMGB1 may be required to prevent hematopoietic stem cell exhaustion to ensure immune homeostasis. In summary, this study showed how HMGB1 is linked to SP and NK-A to protect the most primitive hematopoietic cell and also to maintain immune/hematopoietic homeostasis.
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PMID:Neuroimmune/Hematopoietic Axis with Distinct Regulation by the High-Mobility Group Box 1 in Association with Tachykinin Peptides. 3192 47