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

Whole-cell recordings were made from neurons of the rat locus coeruleus in a tissue slice removed from rat brain. Substance P caused an inward current in cells voltage-clamped at -60 mV. The effect of substance P was concentration-dependent (30 nM-3 microM) and was mimicked by similar concentrations of substance K and neuromedin K. The inward current resulted predominantly from an increase in membrane cation conductance; in potassium-free solutions it reversed polarity at about 12 mV. Substance P also reduced the conductance of an inwardly rectifying potassium current; this action was studied with low external sodium concentration. It is concluded that substance P excites rat locus coeruleus neurons by activating an intracellular transduction pathway leading to both cation conductance increase and potassium conductance decrease.
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PMID:Substance P opens cation channels and closes potassium channels in rat locus coeruleus neurons. 127 60

This study investigated the direct effects of substance P (SP) on ciliary beat frequency of human upper airway mucosa. Human adenoid explant tissue was maintained in serum free culture media, MCDB153. Ciliated epithelial cells were observed with phase-contrast microscopy and ciliary activity was measured using a photometric technique. Oscillations in transmitted light caused by ciliary beating were recorded and modal ciliary beat frequency was determined by fast Fourier transformation. Specimens were treated with SP at concentrations of 10(-4), 10(-5), 10(-6), and 10(-7) mol/L and with equal molar solutions of SP and (D-Pro2,D-Trp7,9)-SP, a SP antagonist. Substance P was found to increase ciliary beat frequency in a dose-dependent manner with a maximum increase of 12.1%. This effect was not seen with solutions containing (D-Pro2,D-Trp7,9)-SP. This suggests that SP exerts a direct stimulatory effect on ciliated cells of the upper airway. Because SP is known to be released in the upper airway in response to chemical irritation, it is presumed that the stimulatory effect of SP on mucosal cells provides a protective mechanism against inhaled irritants.
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PMID:Effect of substance P on ciliary beat frequency in human adenoid explants. 127 1

Quantitative receptor autoradiography using Bolton-Hunter iodinated substance P (SP) was used to localize specific sites in the rat hypothalamus. The amount of SP and neurokinin A (NkA) in extracts from discrete areas of the hypothalamus was measured using specific radioimmunoassays. A high density of SP binding sites was observed in the perimeter of the magnocellular paraventricular and supraoptic nuclei, while the magnocellular nuclei themselves possessed a low receptor density. In control animals, the number of SP binding sites was also low in the arcuate nucleus and the median eminence. Substance P and NkA peptide concentrations were highest in the paraventricular nucleus (PVN), decreasing in the following order: arcuate nucleus (Arc) greater than median eminence (ME) greater than supraoptic nucleus (SON) greater than subfornical organ (SFO). In animals given 340 mmol/l NaCl instead of tap water to drink for 12 days, significant increases in the number of SP binding sites occurred in the medial parvocellular subdivision of the PVN, periamygdaloid cortex, medial preoptic nucleus, Arc, and ME, but other hypothalamic areas were unaffected. In saline-treated animals, significant increases in SP and NkA peptide concentrations were observed in the ME, while in the SFO only the concentration of NkA increased significantly. In the SON, substance P and neurokinin A levels were doubled, whereas in the PVN and Arc no changes in peptide levels were observed. Chronic osmotic stimulation is associated with lowered circulating levels of adrenocorticotropin releasing hormone (ACTH), and the present data further substantiate the hypothesis that hypothalamic tachykinin-containing neuronal terminals are centrally involved in the inhibition of anterior pituitary ACTH release observed during chronic osmotic stimulation.
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PMID:Osmotic regulation of substance P and neurokinin A peptide content and substance P binding sites in distinct hypothalamic nuclei of the rat. 127 30

The effect of synthetic substance P (SP), infused intravenously (IV) in doses of 0.5, 1, or 1.5 pmol/kg-1/min-1 over 60 min, on GH secretion was evaluated in seven healthy men. Substance P tests and a control test with normal saline were randomly performed at weekly intervals. No untoward side effects or changes in blood pressure were observed during SP infusions. Serum GH concentrations did not change when normal saline, the lowest dose, or the middle dose of SP were infused. In contrast, GH levels rose significantly when the highest dose of SP was given, with a mean peak two times higher than baseline. Further studies were performed to test the possible influence of SP on the GH response to GH-RH. For this purpose, seven other healthy men were tested with GH-RH (1 micrograms/kg body weight in an IV bolus) during saline or SP (1.5 pmol/Kg-1/min-1 x 60 min) infusion. The GH-RH induced a significant GH rise, with a mean peak seven times higher than baseline. When subjects were infused with SP, the GH response to GH-RH was greatly enhanced, with a mean peak 12 times higher than baseline. These results demonstrate for the first time in humans that the systemic infusion of SP stimulates GH secretion, and suggest that SP might interact with GH-RH in the stimulation of GH secretion.
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PMID:Intravenously infused substance P enhances basal and growth hormone (GH) releasing hormone-stimulated GH secretion in normal men. 127 34

This study examined interactions between effects of the undecapeptide substance P and norepinephrine and the alpha-adrenoceptor agonist clonidine in the mouse spinal cord. All compounds were injected into the lumbar subarachnoid space, and effects on the tail-flick reflex and the behavioural response to intrathecal substance P were evaluated. The tail-flick response latencies were markedly increased 5-20 min. after intrathecal application of norepinephrine (0.0125-0.1 microgram) or clonidine (0.0125-0.1 microgram). The actions of both intrathecal norepinephrine (0.025 microgram) and intrathecal clonidine (0.025 microgram) were significantly attenuated when substance P (5 micrograms) was given intrathecally 55 and 45 min. before the agonists. There was a significant relationship between the tail-flick response latencies and the tail skin temperature. However, the tail-flick results were not due to changes in the skin temperature. Intrathecally applied substance P (10 ng) produced a response consisting of biting of the caudal part of the body and a few hindlimb scratches. The number of bites was significantly reduced 5 min. after injection of norepinephrine (0.1 micrograms) or clonidine (0.05-0.1 microgram), but the number of scratches was unchanged. The data show that increased stimulation of spinal alpha-adrenoceptors inhibits a spinal nociceptive reflex as well as the action of substance P in the spinal cord. Substance P modulates the action of alpha-adrenoceptor agonists on the tail-flick reflex, which may tentatively be explained by downregulation of alpha-adrenoceptors by substance P.
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PMID:Interactions between substance P and norepinephrine in the regulation of nociception in mouse spinal cord. 127 52

Tachykinin receptors mediating substance P-induced secretion were examined in muscle-stripped segments of guinea-pig ileum set up in flux chambers. Changes in the short-circuit current (Isc) served as an index of active, electrogenic ion transport. Substance P evoked a transient increase in Isc which was concentration-dependent. The maximal change in Isc occurred at 1 microM concentration. [Sar9,Met(O2)11]-substance P, a neurokinin 1 (NK-1) receptor agonist, evoked a similar concentration-dependent increase in Isc. [Nle10]NKA(4-10) (1 microM) or [Pro7]NKB (1 microM), selective NK2 and NK3 agonists, respectively, had minimal effects on Isc. CP-96,345 (5 microM), a nonpeptide NK-1 antagonist, and the peptide NK-1 antagonist, GR82334 (1 microM), reduced the secretory response to substance P (50 nM) in the presence and absence of tetrodotoxin (0.2 microM). The NK2 antagonist, [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) MEN 10207 had no effect on the substance P response. Tetrodotoxin (0.2 microM) significantly reduced, but did not abolish the Isc response to substance P (1 microM) and [Sar9,Met(O2)11]substance P (1 microM). The substance P response was unaltered by 5 microM atropine and 50 microM mecamylamine. Piroxicam (10 microM) or pyrilamine (10 microM) or a combination of both had no effect on the tetrodotoxin-resistant substance P response. Electrical field stimulation evoked a biphasic increase in Isc which was significantly reduced by 0.2 microM tetrodotoxin. Atropine (5 microM) reduced the first peak of the biphasic response and mecamylamine (50 microM) had no effect. Similarly, 5 microM CP-96,345 and 1 microM GR82334 did not alter the EFS-induced change Isc. The results suggest that substance P-evoked secretory responses are independent of histamine or prostaglandins. Substance P responses are mediated by an NK-1 receptor type on enteric neurons and possibly epithelial cells.
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PMID:Neurokinin 1 receptors mediate substance P-induced changes in ion transport in guinea-pig ileum. 127 53

Substance P causes granulocyte (neutrophil and eosinophil) infiltration in mouse skin by inducing mast cell degranulation. However, the mediator responsible for this granulocyte infiltration has not been determined. In this study, we examined the effect of a leukotriene B4 (LTB4) antagonist ONO-4057 on substance P-induced granulocyte infiltration in the skin of BALB/c mice. Pretreatment with the LTB4 antagonist decreased substance P-induced neutrophil and eosinophil infiltrations in mouse skin at 6 h to the same extent that an inhibitor of mast cell degranulation disodium cromoglycate decreased those responses. The LTB4 antagonist also decreased substance P-induced neutrophil, but not eosinophil, infiltration in mouse skin at 24 h. We conclude that LTB4 is a major mast cell-derived chemotactic mediator for initiating substance P-induced neutrophil and eosinophil infiltrations in mouse skin.
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PMID:[Effect of a leukotriene B4 antagonist on substance P-induced granulocyte infiltration in mouse skin]. 128 87

A novel method for detecting the membrane receptors of Substance P (SP) has been developed. The method does not require radioactive derivatives of SP and is based on quantitation of specifically bound biotinylated SP (Bt-SP), the analysis being performed after destruction of the ligand-receptor complex in acidic conditions and Bt-SP extraction into solution. The acidic extract from the Bt-SP-membrane complex after neutralization is added to immulon microELISA plate coated with affinity purified anti-SP-antibodies. The sensitivity of subsequent detection of Bt-SP enhances by using a new type of the streptavidin conjugate with a polymeric form of horseradish peroxidase. Enzyme immunoassay conditions were optimized using [125I]-labelled SP derivative. The developed method allows the determination of femtomoles of SP in a sample and has a sensitivity comparable to that of radioligand analysis.
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PMID:[A new immunochemical method for detecting substance P receptors based on the biotin-streptavidin system]. 128 Jan 42

Substance P (SP) infused into the third cerebral ventricle blocks spontaneous ovulation in female rats, probably through catecholaminergic neurons. The studies presented in this paper were undertaken to investigate whether SP exerts its suppressing effect on ovulation in 6-hydroxydopamine (6-OHDA) pretreated female rats. After 8-12 days following 6-OHDA pretreatment female rats were infused, on the day of proestrus, with vehicle and all animals were found to ovulate or with a solution containing 5 nmol of SP and 89% of female rats were then found to ovulate. In the group pretreated with vehicle and subsequently infused with SP, ovulation was found to occur only in 25% of animals. The obtained results indicate that spontaneous ovulation in 6-OHDA-pretreated female rats cannot be blocked by i.c.v. administration of SP, and it may be concluded that SP exerts its suppressing effect through the monoaminergic neurons.
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PMID:Occurrence of ovulation after intracerebroventricular infusion of substance P in 6-OHDA pretreated female rats. 128 Apr 86


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