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)

Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.
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PMID:UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms. 128 76

We examined the role of the potent vasoactive kinin substance-P (SP) in flushing derived from various causes. SP was measured in plasma after acetone/ether extraction using an antiserum directed at the carboxy-terminal 5-11 amino acid region of undecapeptide SP. The antiserum had less than 1% cross-reaction with the other neurokinins, neurokinin-A and neuropeptide-K, that derive from the beta-preprotachykinin gene and share carboxy-terminal residues. Basal and pentagastrin-stimulated SP levels were measured in 22 healthy controls, 11 patients with histologically proven carcinoid tumors, 8 patients with tumors other than carcinoid, and 7 patients with idiopathic flushing (IF). Basal SP levels were less than 10 pg/mL in normal subjects. All patients with midgut carcinoid tumors had SP levels greater than 25 pg/mL, as did 7 of 8 patients with noncarcinoid tumors and 5 of 7 patients with IF. Using 50 pg/mL as the cutoff point, the sensitivity was 63% for detection of a tumor, and 100% of nontumor patients were excluded. Pentagastrin administration uniformly induced flushing and caused a rise in SP levels greater than 150 pg/mL in 5 of 10 patients with carcinoid tumors, 3 of 8 with noncarcinoid tumors, and 0 of 7 with IF, i.e. a SP rise of more than 100 pg/mL suggests a tumor. Administration of somatostatin (150 micrograms) 0.5 h before the pentagastrin abolished flushing in all carcinoid patients and reduced SP levels, but not into the normal range. Long term treatment with SMS significantly reduced flushing and lowered SP levels, but did not restore these to normal. We conclude that 90% of patients with carcinoid/noncarcinoid tumor have raised COOH-terminal SP levels. A basal level above 50 pg/mL or a pentagastrin-stimulated rise of more than 100 pg/mL distinguishes carcinoid from IF. The dissociation between SP concentrations and flushing suggests that SP may not be the only kinin involved in the flushing associated with carcinoid tumors.
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PMID:Plasma substance-P in neuroendocrine tumors and idiopathic flushing: the value of pentagastrin stimulation tests and the effects of somatostatin analog. 169 75

Rats chronically implanted with intrathecal catheters received intrathecal injections (10 microliters followed by 10 microliters saline flush) of either saline (n = 5), somatostatin (100 micrograms, n = 10), the somatostatin analog BIM 23003 (100 micrograms, n = 5), the somatostatin analog SMS 201-995 (100 micrograms, n = 5), the substance P analog [D-Pro2, D-Trp7,9] SP (10 micrograms, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.
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PMID:Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats. 171 Nov 72

The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT from tumour cells. The DNA contents of cultures were not affected by SMS (10(-8) M or 10(-10) M) treatment for 4 or 14 days. When tumour cell cultures were challenged with isoprenaline (IP) (10(-6) M) no reduction of the IP induced release of 5-HT could be detected after pretreatment of tumour cell cultures with SMS (10(-8) M) for 1 h, 4 h or 4 days. These studies provide evidence for a direct action of the somatostatin analogue on midgut carcinoid tumour cells, reducing both synthesis and secretion of hormones from tumour cells. This effect appears not to be related to inhibition of tumour cell growth. The inhibition of 5-HT secretion from tumour cells by SMS seems to operate via a second messenger system different from the one mediating the beta-adrenoceptor stimulated release of 5-HT.
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PMID:The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells. 171 51

The interactions between vasoactive intestinal peptide (VIP), substance P (SP), a somatostatin analog (SMS 201-995) and dexamethasone have been investigated on the Con A mitogenic response of rabbit spleen cells. The neuropeptide regulatory effects appeared to be time dependent: when added with the Con A mitogen, they inhibited (VIP) or did not modulate (SMS and SP) the rabbit lymphocyte proliferation and did not change the inhibitory effect induced by a dexamethasone preincubation. When added 18 h before the mitogen, they all induced an increase of the proliferative response at high concentration. The mitogenic response observed when adding dexamethasone to lymphocytes previously preincubated in the presence of neuropeptides was not different from control response except with SMS 10(-10) M. The similar lymphocyte responses obtained whatever the neuropeptide suggested that the immunomodulatory effect induced by a neuropeptide preincubation might be mediated by the induction of common effector(s).
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PMID:Interactions between neuropeptides and dexamethasone on the mitogenic response of rabbit spleen lymphocytes. 171 58

Nine patients with pancreatic apudomas (seven gastrinomas, one glucagonoma, one tumor secreting a substance P-like component) and nine with metastasized carcinoid tumors were treated with a somatostatin analogue (SMS 201-995), administered subcutaneously twice daily for 3 days. Treatment was pursued for 2 to 12 months in nine patients in whom SMS was clinically and/or biologically beneficial. In gastrinomas, SMS decreased plasma gastrin in all but one patient, inhibited the residual gastric acid secretion under H2-blockers and improved diarrhea; in the glucagonoma patient, glucagonemia decreased and skin lesions disappeared. In carcinoid syndrome, clinical efficacy was partial and inconstant; daily 5-hydroxyindole acetic acid (5-HIAA) output was slightly decreased. Plasma substance P levels decreased in six patients with initially high concentrations. No antitumoral activity or side effects have been so far evidenced. SMS 201-995 is a useful, well-tolerated agent in secreting pancreatic apudomas and to a lesser extent in carcinoid syndrome, where high-dosage regimens may be required.
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PMID:Clinical and hormonal effects of a long-acting somatostatin analogue in pancreatic endocrine tumors and in carcinoid syndrome. 243 3

Antisera of defined regional specificity have been used to measure the concentration of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) during a meal-induced flush in 10 patients with metastatic carcinoid tumours. Although all patients flushed, NKA-LI levels in five patients and SP-LI in six patients were not elevated relative to healthy subjects (NKA-LI, less than 3 pg/ml; SP-LI, less than 10 pg/ml) both in the fasted state and after food. In the patients with elevated basal plasma tachykinin levels, increases in NKA-LI and SP-LI after food were erratic and did not correspond to a defined digestive phase or the occurrence of the flush. Chromatographic analysis of plasma demonstrated the presence of neuropeptide K and neurokinin A, and the detection of COOH-terminal fragments of substance P is consistent with the higher levels of circulating SP-LI measured with a COOH-terminally directed antiserum compared with an NH2-terminally directed antiserum. Subcutaneous injection of the somatostatin analogue SMS 201-995 (50 micrograms) alleviated symptoms of flush in two of three patients but only partially suppressed NKA-LI and SP-LI concentrations. It is concluded that circulating tachykinins cannot be solely responsible for the meal-induced carcinoid flush.
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PMID:Circulating tachykinins (substance P, neurokinin A, neuropeptide K) and the carcinoid flush. 288 98

The proinflammatory peptide substance P (SP) has been shown to be intimately involved in the local inflammatory processes of Trichinella-spiralis-induced murine intestinal inflammation. Significant increases in SP, increased myeloperoxidase levels coupled with local morphological deterioration of the jejunum and impaired lymphocyte responses to exogenous SP in vitro have been associated with the model. We have recently determined that the elimination of increased levels of SP via anti-SP antibody therapy can spare the murine gastrointestinal tract much of the pathologies associated with the parasitic infection. Here we further demonstrate that the somatostatin analogue SMS 201-995 as well as the SP receptor antagonist CP 96,345 can effectively decrease the inflammation and lost lymphocyte function seen in the jejunum of T. spiralis-infected mice. Again, both intestinal morphology and myeloperoxidase levels were shown to return to normal values upon treatment. The above results suggest that SP is an important modulator of gastrointestinal inflammation.
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PMID:Substance-P-mediated intestinal inflammation: inhibitory effects of CP 96,345 and SMS 201-995. 754 31

Long-acting somatostatin analogue (SMS 201-995) inhibits serotonin, bradykinin, prostaglandins, substance P, and vasoactive intestinal peptide, which may be involved in migraine. We therefore decided to test the efficacy of SMS 201-995 in relieving the pain of acute migraine attacks. Headache relief was defined as a reduction in severity from grade 3 or 2 (severe or moderate) to 1 or 0 (mild or none). Patients experiencing migraine attacks were evaluated clinically. A double-blind parallel group trial was performed in which patients randomly received either a subcutaneous injection of placebo (saline) or SMS 201-995 (100 micrograms). SMS 201-995 was significantly more effective than placebo in reducing headache grade at 2 h (1.5 +/- 0.6 vs 2.2 +/- 0.7; p < 0.01), 4 h (1.5 +/- 0.6 vs 2.1 +/- 0.8; p < 0.05) and 6 h (0.8 +/- 0.9 vs 2.1 +/- 0.8; p < 0.001) after the initiation of treatment. By 6 h, apparent headache relief (reduction in severity from grade 3 or 2 to 1 or 0) was experienced in 76.5% of SMS 201-995 treated patients and 25% of the placebo-treated group. Headache relief was significantly better in patients taking SMS 201-995 (p < 0.02). Furthermore, none of the patients became pain-free (headache grade 0) on placebo, while significantly more patients (47%) were pain-free on SMS 201-995 at 6 h (p < 0.01). Headache improvement started significantly earlier in those patients treated with SMS 201-995 than with placebo. SMS 201-995 significantly improves the pain of migraine attacks, 2 h after the beginning of treatment. Additionally, we observed no side effects of SMS 201-995. We therefore conclude that a single dose of 100 micrograms given subcutaneously is an effective and well-tolerated agent for the treatment of migraine attacks.
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PMID:Treatment of migraine attacks with a long-acting somatostatin analogue (octreotide, SMS 201-995). 905 32