Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighteen patients with chronic pain syndromes of organic origin were treated by means of high frequency transcutaneous nerve stimulation (hi-TNS). The CSF levels of receptorassayable Fraction I and II endorphins, substance P-like immunoreactivity (SPLI), and the monoamine metabolites 5-HIAA, HVA and MOPEG were measured before and after one week of daily treatment. Furthermore, the effects on experimental pain measures were determined. The therapeutic effect was evaluated after 30 days and 3 months of treatment. Patients with low initial concentrations of endorphins in CSF, lower than those observed in healthy volunteers, tended to have the best response to hi-TNS. There were significant increases in Fraction I endorphins and SPLI in CSF, most pronounced in the patients who responded. There were no significant changes in 5-HIAA, HVA or MOPEG in CSF. However, in early responders, the serotonin metabolite 5-HIAA tended to decrease as contrasted to an increase in non-responders. The difference between the groups was statistically significant. Confirming our earlier studies, the therapy induced changes in pain measures showed a significant, positive correlation with increasing Fraction I endorphins in CSF. Our results suggest that hi-TNS induces central changes in the endorphinergic, serotonergic and possibly substance-P-ergic systems.
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PMID:Long-term high frequency transcutaneous electrical nerve stimulation (hi-TNS) in chronic pain. Clinical response and effects on CSF-endorphins, monoamine metabolites, substance P-like immunoreactivity (SPLI) and pain measures. 241 23

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 monoaminergic innervation of the central nervous system (CNS) is characterized by long and short projecting neurons. The neurological correlates of diabetes are usually referred to as processes of degenerative atrophy affecting motor and sensory peripheral nerves. We have found that the long serotoninergic axons innervating the spinal cord and the cerebral cortex are unaffected in diabetic animals and that the noradrenergic innervation of the cortex is normal as well. The serotonin content is doubled in the hypothalamus with no apparent alteration of 5-HIAA levels, suggesting a supernumerary innervation that is accompanied by a reduced release. In pons medulla oblongata, serotonin and dopamine with the relative metabolites 5-HIAA and DOPAC are significantly reduced, whereas noradrenaline is markedly increased. In the hippocampus, there is a reduction of serotonin content. The serotoninergic alterations are peculiar as suggested by the sparing of the most distal projections that is accompanied by hyperinnervation of the hypothalamus and the loss of shorter collaterals in the pons medulla oblongata. In the hypothalamus and in the striatum of diabetic rats, there are significant higher levels of substance P and met-enkephalin, respectively. The abundance of proenkephalin A mRNA is also increased in the striatum. Conversely, in the lumbar cord of diabetic animals, the levels of substance P and met-enkephalin are significantly reduced. Such alterations likely reflect retrograde degeneration of the peripheral sensory input. The CNS changes are unlikely due to vascular abnormalities in the brain of diabetic rats; rather, we suggest that the persistent lack of insulin is the major factor involved as a trigger of the monoaminergic changes in the diabetic brain.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals. II. Monoaminergic and peptidergic alterations in the diabetic encephalopathy. 248 Apr 54

N-terminally extended substance P (SP) and neuropeptide K (NPK), an N-terminally extended form of neurokinin A (NKA), were determined in cerebrospinal fluid (CSF) from healthy human subjects by combined high performance liquid chromatography and radioimmunoassay. The concentrations of the peptides were similar in fresh CSF and in CSF which had been kept frozen for up to 5 months. SP and NKA were not present in measurable amounts in neither fresh CSF nor in CSF that had been frozen. On the other hand, when synthetic SP and NKA were added to approx. 2 pM concentration to fresh CSF samples, both peptides were recovered to 85 and 98%, respectively. There were no significant concentration gradients of the peptides in the first 18 ml (three consecutive 6 ml fractions) of CSF (n = 10). In contrast, we confirmed previous findings, that there are gradients of the amine metabolites 5-HIAA (P < 0.01) and HVA (P < 0.001) (n = 5). The concentrations of extended SP (expressed in SP equivalents) and NPK in the first 6 ml of CSF were 1.5 +/- 0.7 pM and 14.2 +/- 6.4 pM (mean +/- S.D., n = 10), respectively. The present results thus show that the levels of N-terminally extended SP and NKA are stable in frozen CSF samples for up to 5 months. The virtual lack of SP and NKA in CSF does not seem to be due to losses during sample preparation or storage.
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PMID:Quantitation of N-terminally extended tachykinins in cerebrospinal fluid from healthy subjects. 751

Electric stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to conventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. opioids, serotonin, noradrenaline, substance P, GABA), have been proposed to be involved in the pain-alleviating effect of SCS. However, as yet there is no evidence that these would be involved in the beneficial effects of SCS. We have studied neurotransmitter release, using microdialysis techniques, in the spinal dorsal horn and the periaqueductal grey substance (PAG) of the rat and the cat, induced by SCS applied with current parameters equivalent to those used clinically in man. Up to now dialysates have been assayed for GABA, serotonin and substance P with highly sensitive methods. Three groups of studies have been carried out: (1) dorsal horn microdialysis in rats under halothane anesthesia during acute SCS; (2) dorsal horn microdialysis in cats under barbiturate anesthesia or following decerebration, and (3) PAG microdialysis in awake, unrestrained rats with chronic SCS. In the dorsal horn studies, microdialysis probes of different sizes were implanted in the lower lumbar dorsal horns. In the PAG studies, rats had guide cannulas for microdialysis stereotactically inserted into the PAG. SCS was applied at a low thoracic level with 50 or 100 Hz; 0.2 ms and an intensity amounting to 2/3 of the motor threshold. The microdialysis probes were perfused with modified Ringer's solution. Fractions of the dialysate were collected at various intervals. GABA and serotonin were assayed by reverse-phase HPLC, while substance P was investigated using a highly sensitive radioimmunoassay. SCS induced a significant release of GABA in the dorsal horn, most marked in the fraction following the stimulation period. In the rats with PAG microdialysis, the GABA level decreased significantly following two stimulation periods, although transitional increases during SCS were noted in some animals. In the decerebrated cat, a significant release of serotonin in the dorsal horn was obtained with SCS, while the levels of the metabolite 5-HIAA were little influenced by stimulation. On the contrary, in the decerebrated preparation there was no release of substance P in the dorsal horn with SCS, although in the intact cat under barbiturate anesthesia a significant release was induced.4+ off
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PMID:Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and recent experimental studies. 753 60

Unlike rats, but similar to primates, guinea pigs exhibit prolonged function of the corpus luteum and elevated progesterone secretion after ovulation. The gonadotropins, estrogen (E) and progesterone (P) have been examined throughout the guinea pig estrous cycle. However, neither prolactin secretion nor its regulation by steroid hormones has been characterized, perhaps due to the lack of a specific radioimmunoassay. beta-Endorphin (BE), substance P (SP), and serotonin (5-HT) increase prolactin secretion in rats and monkeys. BE and SP neurons in guinea pigs and 5-HT neurons in monkeys contain progestin receptors which could mediate neuroendocrine effects of steroid hormones. Therefore, the effects of E and P on prolactin, BE, SP, and 5-HT and its metabolite 5-HIAA were examined in guinea pigs which were ovariectomized, E treated (28 days), and E+P treated (14 days E+14 days E+P). The rat NB2 lymphoma cell line was used as a bioassay for serum prolactin. BE and SP levels were measured by radioimmunoassay in four hypothalamic areas: the preoptic region (POA), the mediobasal hypothalamus (MBH), the dorsomedial hypothalamus (DMH), and the mamillary bodies (MB). 5-HT and 5-HIAA were measured in the midbrain raphe area by high-pressure liquid chromatography. E alone had little effect on serum prolactin levels, but E+P significantly increased prolactin as compared with ovariectomized controls. The BE levels increased with E treatment and remained elevated with E+P treatment in MBH and POA. The BE content was stimulated in DMH and MB by E+P treatment and not with E alone. The SP content in MBH, DMH, and MB increased in E-treated guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of progesterone on prolactin, hypothalamic beta-endorphin, hypothalamic substance P, and midbrain serotonin in guinea pigs. 754 80

Neuroendocrine gut and pancreatic tumors are known to contain and secret different peptide hormones and amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful biochemical markers from the clinical point of view. The glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various neuroendocrine tumors, both by histopathology and circulating tumor markers. In patients with demonstrable endocrine tumors, about 90 percent of the patients present high circulating levels of chromogranin A. A hundred-fold increase of plasma chromogranin is seen in patients with midgut carcinoid tumors and liver metastases. The plasma levels of chromogranin A reflect the tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the chromogranin A might be an indicator of bad prognosis in patients with malignant carcinoid tumors. Besides analyzing plasma chromogranin A, specific analyses such as urinary 5-HIAA in midgut carcinoid patients, serum gastrin in patients with Zollinger-Ellison syndrome and insulin/proinsulin in patients with hypoglycemia should be performed. In patients with small tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test, secretin test or pentagastrin stimulation of tachykinin release can supplement the basal measurements of peptides and amines. To fully evaluate the growth potential in neuroendocrine tumors, traditional biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the PDGF-alpha receptor. Finally, analysis of somatostatin receptor subtypes and induction of the enzymes 2-5A syntethase and PKR are of clinical value.
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PMID:Biochemical diagnosis of neuroendocrine GEP tumor. 982 77

The substance P/NK1 receptor system plays an important role in the regulation of stress and emotional responding and as such had been implicated in the pathophysiology of anxiety and depression. The present study investigated whether alterations in the substance P/NK1 receptor system in brain areas which regulate emotional responding accompany the depressive behavioural phenotype observed in the olfactory bulbectomised (OB) mouse. The effect of NK1 receptor deletion on behavioural responding and monoamine levels in discrete brain regions of the OB model, were also examined. Substance P levels in the frontal cortex and NK1 receptor expression in the amygdala and hippocampus were enhanced following olfactory bulbectomy. Although NK1 receptor knockout (NK1-/-) mice did not exhibit altered behavioural responding in the open field test, noradrenaline levels were enhanced in the frontal cortex, amygdala and hippocampus, as were serotonin levels in the frontal cortex. Locomotor activity and exploratory behaviour were enhanced in wild type OB mice, indicative of a depressive-like phenotype, an effect attenuated in NK1-/- mice. Bulbectomy induced a decrease in noradrenaline and 5-HIAA in the frontal cortex and an increase in serotonin in the amygdala, effects attenuated in OB NK1-/- mice. The present studies indicate that alterations in substance P/NK1 receptor system underlie, at least in part, the behavioural and monoaminergic changes in this animal model of depression.
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PMID:Neurokinin-1 receptor deletion modulates behavioural and neurochemical alterations in an animal model of depression. 2215 76