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)

Gut-associated lymphoid cells are modulated by several gut hormones. We postulated that lymphokine-associated-killer (LAK) cell cytotoxicity of lymphocytes isolated from the gut mucosa may be increased by substance P (SP). Intestinal lamina propria mononuclear cells (LPMC) and colonic cancer cells were isolated from operative specimens by successive mechanical and enzymatic dissociation methods. Effector LAK cells were induced by culturing LPMC with recombinant interleukin-2 at a concentration of 250 U/ml. Substance P (10(-5) M) was added to the culture medium. Targets consisted of fresh colon cancer cells, HT-29 (cultured human colon cancer cell line), and control cell lines. After 4 days of incubation, cytotoxicity was measured using a 4-h 51Cr release assay. LAK cells alone showed moderate cytotoxicity against HT-29 and none against fresh colon cancer cells. LAK cells generated in the presence of substance P showed moderate cytotoxicity against HT-29 and strong cytotoxicity against fresh colorectal cancer cells. The percentage of cytotoxicity +/- SEM at various effector to target ratios was [(*) denotes P < 0.05 compared with above]: [table: see text] We conclude that substance P significantly increases LAK cell cytotoxicity against fresh colon cancer cells, but not against cultured cells.
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PMID:Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells. 127 74

The effects of electrical field stimulation (EFS) of rabbit middle cerebral arteries were examined using wire-mounted arterial segments. EFS of segments maintained at rest tension caused a tetrodotoxin-sensitive sympathetic contraction. In agonist-contracted segments maintained at approximately 60% of tissue maximum force, EFS caused a relaxation in two thirds of the preparations. Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS relaxation was tetrodotoxin-sensitive but was not blocked by either chronic surgical sympathectomy or exposure to guanethidine (5 microM). Electron microscopy of chromaffin-fixed arterial sections showed the presence of chromaffin-positive large and small vesicles. Within the same sheath of Schwann were also a smaller number of nerve profiles containing many small clear vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM) eliminated the EFS relaxation in approximately 50% of the segments and reduced the response in another 35-40%; in the remainder, relaxation was unaffected. Combined data for endothelium removal and atropine treatment showed that each caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine also significantly reduced EFS relaxation in guanethidine-treated segments. There was no reduction in EFS relaxation after procedures that antagonized ATP- or substance P-mediated relaxations. These results indicate that EFS of precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic relaxation. The neuroeffector mechanism mediating this response has a predominantly cholinergic endothelium-dependent component as well as a noncholinergic endothelium-independent component.
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PMID:Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery. Evidence of a cholinergic endothelium-dependent component. 134 15

Substance P is a neuropeptide that has been identified in the ovary, fallopian tube, uterus, and vagina and in the hypothalamic-pituitary axis in both an animal model and human ovaries. We sought to determine if substance P is present in peritoneal fluid and, if so, whether it correlated with the cause of infertility. Its presence was determined by radioimmunoassay in the peritoneal fluid of 66 patients undergoing diagnostic laparoscopy for clinical indications related to infertility. Total volume of peritoneal fluid and cycle day were recorded; patients were evaluated in groups according to diagnosis: endometriosis (n = 24), pelvic adhesions (n = 18), and normal controls (n = 24). The level of substance P (mean +/- SEM) was 122 +/- 19 pg/ml for endometriosis and 130 +/- 19 pg/ml for pelvic adhesions. These values were not significantly different from the normal controls (130 +/- 25 pg/ml). There was no significant difference in levels between follicular and luteal phase of the menstrual cycle. We conclude that substance P is present normally in peritoneal fluid and that its levels are not affected by pelvic endometriosis or adhesions.
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PMID:Substance P in peritoneal fluid. 137 Jul 40

The local production of autocrine or paracrine agents in endocrine tissues represents an important level of hormonal regulation. The synthesis of neuropeptide-Y (NPY), substance-P (SP), and vasoactive intestinal peptide (VIP) in the rat anterior pituitary gland has been well demonstrated. We have now studied their expression in human postmortem pituitary tissue. Northern blot analysis of poly(A)+ RNA from whole human pituitaries revealed mRNA encoding the precursors for NPY, SP, and VIP whose hybridization characteristics were indistinguishable from those of the same mRNAs described in previously characterized human tissues. VIP mRNA was detectable in all samples tested, with NPY and preprotachykinin-A mRNA (which encodes SP) detectable in a subset of the pituitaries. The concentration of immunoreactive NPY in whole human pituitary was 3.8 +/- 1.1 pmol/g wet wt in males and 2.9 +/- 0.5 pmol/g wet wt in females (mean +/- SEM; n = 10), that of SP was 3.1 +/- 0.4 pmol/g wet wt in males and 5.2 +/- 1.3 pmol/g wet wt in females (n = 10), and that of VIP was 8.1 +/- 2.9 pmol/g wet wt in males and 5.3 +/- 1.6 pmol/g wet wt in females (n = 10). Size-fractionation of pituitary extracts by gel permeation chromatography revealed single peaks of NPY and VIP-like immunoreactivity in the positions of the standards, while SP-like immunoreactivity mostly eluted in the position of synthetic SP, with two minor immunoreactive peaks eluting earlier. The low levels of NPY, SP, and VIP and their mRNAs in the human pituitary are consistent with peptides having an autocrine/paracrine, rather than endocrine, mode of action.
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PMID:Expression of messenger ribonucleic acids encoding neuropeptide-Y, substance-P, and vasoactive intestinal polypeptide in human pituitary. 138 56

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.
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PMID:Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise. 139 15

In the present study, we investigated whether an established method of cryostorage at -75 degrees C in the presence of dimethyl sulfoxide (Me2SO) and fetal calf serum (FCS) could preserve the vascular and endothelial responses of isolated human coronary arteries. A total of 123 ring segments (4-5 mm in length) of epicardial coronary arteries were isolated within 1 to 2 h from hearts of four patients receiving a cardiac transplant. Thirty-nine coronary ring segments were studied immediately upon cleaning of surrounding tissues, while 84 similarly cleaned segments were stored at -75 degrees C for 7 to 10 days prior to in vitro reactivity studies. In the freshly isolated coronary arteries, addition of prostaglandin F2 alpha, endothelin (ET-1), or acetylcholine consistently produced a dose-dependent contraction, reaching a maximum contractile force of 9.6 +/- 0.7, 4.5 +/- 0.5, and 3.1 +/- 0.5 g (M +/- SEM), respectively, while histamine, thrombin and substance P consistently produced an endothelium-dependent relaxation (EDR) with a maximum of -89 +/- 2.8, -85 +/- 5.0, and -72 +/- 3.5%, respectively. Isoproterenol produced an endothelium-independent relaxation (-82 +/- 4.5%). Cryostorage of human coronary arteries at -75 degrees C without cryoprotectant resulted in a complete loss of the contractile response. In contrast, addition of Me2SO and FCS in the cryostorage medium significantly preserved the contractile responses, although they were decreased (1.9 +/- 0.3, 1.5 +/- 0.3, and 0.6 +/- 0.1 g to PGF2 alpha, ET-1, and acetylcholine, respectively) when compared to the fresh controls. The maximum EDR to histamine, thrombin, and substance P in the cryostored coronaries were also reduced to -40 +/- 5.6, -21 +/- 3.3, and -47 +/- 4.7%, respectively, and the isoproterenol-induced relaxation was reduced to -62 +/- 4.1%. These results suggest that although the cryostorage method described in the present report provided only limited preservation of human coronary arteries, significant vascular smooth muscle and endothelial-dependent functions were retained. Thus, it is possible that further refinement of the present cryostorage methodology may provide better preservation of functionally viable human blood vessels.
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PMID:Human coronary vascular smooth muscle and endothelium-dependent responses after storage at -75 degrees C. 158 28

The maturation of the neuromodulatory action of substance P (SP) was investigated in tracheal smooth muscle (TSM) segments isolated from rabbits aged 2-24 wk. The tissues were placed in baths containing Krebs-Ringer solution and contracted with electrical field stimulation (ES) with ES frequencies ranging from 1 to 75 Hz. In tissues greater than 1 mo of age, the ES frequency-response relationships were progressively shifted in the presence of a maximally effective neuromodulatory SP dose (10(-7) M) such that by 24 wk of age the mean (+/- SEM) maximal tension (Tmax) significantly increased from 380.4 (+/- 41.9) to 502.3 (+/- 64.2) g/g TSM, and the corresponding mean (+/- SEM) log ES frequency producing 50% of Tmax (log ES50) significantly decreased from 1.209 (+/- 0.069) to 1.055 (+/- 0.046) Hz. By contrast, relative to methacholine, the direct contractile effects of SP did not significantly vary with age. In further analyzing the basis for the above age-related difference in the neuromodulatory action of SP, we found that the magnitude of SP-induced neuromodulation was highly correlated to the tissue's intrinsic sensitivity to ES. Indeed, after accounting for the tissue's sensitivity to ES, the effect of age alone on the magnitude of SP-induced neuromodulation was not statistically significant. These findings provide new evidence that: (a) SP-induced neuromodulation of acetylcholine release at the airway neuromuscular junction is significantly enhanced during postnatal development; and (b) that the latter age-dependent action of SP is based on a close coupling of the magnitude of SP-induced neuromodulation to the tissue's intrinsic sensitivity to neurally mediated contraction.
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PMID:Maturation of neuromodulatory effect of substance P in rabbit airways. 168 82

Endothelin-1 is a 21 amino acid peptide originally isolated from porcine aortic endothelium and has recently been localized within the central nervous system. We have administered endothelin-1 in a dynamic perfusion system in order to study its possible effects on the rat hypothalamus and anterior pituitary. Tissue (hypothalami or quartered pituitaries) was placed into plastic chambers and was perfused with oxygenated Krebs-bicarbonate solution. After an interval to establish stable basal peptide release, endothelin-1 was administered at two doses (0.1 and 1 microM) and the release of substance P, vasoactive intestinal peptide, 7B2, and somatostatin was measured, the last being detectable only in hypothalamic perfusates. Both concentrations of endothelin-1 led to a significant increase (P less than 0.01) in the release of substance P from the hypothalamus and pituitary, but not of vasoactive intestinal peptide, 7B2, or somatostatin. Thus after the 0.1 microM and 1 microM endothelin-1 perfusion substance P release from the hypothalamus increased by 125 +/- 5% and 215 +/- 15% (mean +/- SEM) of basal and from the pituitary by 168 +/- 8% and 276 +/- 15% (mean +/- SEM). No change occurred in the output of ACTH or other pituitary hormones. The release of substance P from hypothalamus or pituitary after stimulation with endothelin-1 was not blocked when a calcium free medium was used. Endothelin-1 binding sites were identified on rat pituitary cell membranes. These findings suggest the possibility that endothelin may act as a paracrine substance, neurotransmitter, or neuromodulator in the hypothalamo-pituitary axis.
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PMID:Release of substance P from rat hypothalamus and pituitary by endothelin. 169 95

In this study, we examined whether inhalation of hypertonic saline aerosols increases vascular permeability in the rat trachea, and we examined the role of neurogenic inflammation in this response. Stereological point counting was performed to measure the percent area occupied by Monastral blue-labeled blood vessels as a means of quantifying the increase in vascular permeability in tracheal whole mounts. Hypertonic saline aerosols (3.6-14.4% NaCl) increased vascular permeability in a dose-dependent fashion compared with 0.9% NaCl. Thus, the area density of Monastral blue-labeled vessels after inhalation of 3.6% NaCl was greater (21.2 +/- 3.5% mean +/- SEM, n = 5) than after 0.9% NaCl aerosol (3.3 +/- 0.9%, n = 5, P less than 0.5). The neutral endopeptidase inhibitor phosphoramidon (2.5 mg/kg, i.v.) significantly potentiated the increase of vascular permeability caused by 3.6% NaCl. Desensitization of sensory nerve endings by pretreatment with capsaicin markedly reduced the usual increase in vascular permeability caused by 3.6% NaCl, but the increase in vascular permeability induced by aerosolized substance P (10(-4) M) was unchanged. These findings suggest that hypertonic saline increases vascular permeability in the rat trachea by stimulating the release of neuropeptides from sensory nerves.
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PMID:Hypertonic saline increases vascular permeability in the rat trachea by producing neurogenic inflammation. 169 78

We have previously found that antigenic stimulation of mast cells in the guinea pig superior cervical ganglion leads to membrane depolarization of principal neurons and a long-term increase in the efficacy of ganglionic transmission. In this study experiments were conducted to discern the histological, immunological and pharmacological characteristics of the mast cells within the superior cervical ganglion. Mast cells within the superior cervical ganglion could be stained with toluidine blue or berberine sulfate, the latter indicating that heparin-like molecules were present in the granules. Stainable mast cells were distributed throughout the ganglion with no gross evidence of regional localization. The number of mast cells stained with toluidine blue was reduced significantly (P less than 0.01) in contralateral ganglia that had been exposed to the sensitizing antigen (ovalbumin), indicating antigen-induced degranulation. The superior cervical ganglion contained 208 +/- 6 picomole of histamine (mean +/- SEM, n = 66). Ovalbumin evoked the release of histamine from the superior cervical ganglion in a concentration-dependent fashion. At maximally effective concentrations, ovalbumin released 33 +/- 2% of the total histamine stores (mean +/- SEM, n = 61). Similar values were obtained with antigen-challenged stellate ganglia. A temperature of 37 degrees C and an extracellular calcium concentration of 1 mM was required to elicit optimal antigen-induced responses. In addition to releasing histamine, antigenic stimulation of the ganglion resulted in a 3- to 5-fold increase in the synthesis and release of arachidonic acid metabolites including peptidoleukotriene, thromboxane B2, prostaglandins (PG) E2, F2 alpha, D2, the PGD2 metabolite 9 alpha 11 beta-PGF2, and the prostacyclin metabolite 6-keto PGF1 alpha. Various putative mast cell secretagogues were examined for their ability to activate the superior cervical ganglion mast cell, as indicated by evoked histamine release. In contrast to rat peritoneal mast cells, high concentrations of substance P, compound 48/80, and nerve growth factor failed to stimulate the ganglion mast cells. Preganglionic nerve stimulation, electrical field stimulation of axons and cell bodies, or depolarizing concentrations of potassium chloride also failed to activate the superior cervical ganglion mast cells. These results suggest that substances released by membrane depolarization do not influence the function of the resident mast cells. The results demonstrate that the mast cells within sympathetic ganglia can be actively sensitized to respond to specific antigen. These mast cells are similar to lung parenchymal mast cells with respect to histological, immunological and pharmacological characteristics...
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PMID:Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment. 169 91


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