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 localisation and colocalisation of neuronal isoform (type I) nitric oxide synthase, endothelin-1, arginine-vasopressin and substance P in endothelial cells of rat coronary and femoral arteries was investigated by pre-embedding and postembedding immunocytochemistry. Nitric oxide synthase appeared in a high proportion of endothelial cells of both arteries (about 89% in the femoral artery, examined with the preembedding avidin-biotin-peroxidase method, and in almost all cells of the coronary artery, examined with the postembedding immunogold technique). Double immunogold labelling in single cells demonstrated the colocalisation of nitric oxide synthase with endothelin-1, arginine-vasopressin and substance P. The immunolabelling was mostly confined to the cytoplasmic matrix. It is suggested that nitric oxide synthase/nitric oxide and the peptides examined may be involved in local control of blood flow in coronary and femoral arteries.
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PMID:Localisation of nitric oxide synthase and its colocalisation with vasoactive peptides in coronary and femoral arteries. An electron microscope study. 752 54

The hypothesis tested was that inhibition of the L-arginine-nitric oxide (NO) pathway may represent a potential central mechanism of action for acetaminophen (paracetamol). Spinal administration of N-methyl-D-aspartate (NMDA, 0.5 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.1 nmol) or substance P (SP, 0.5 nmol) to the rat provoked a specific behaviour characterized by biting, scratching and licking (BSL). This behaviour was antagonized by pretreatment with acetaminophen for NMDA and SP but not for AMPA. Further, the antinociceptive effect of acetaminophen was readily reversed by administration of the natural substrate for nitric oxide synthase (NOS), L-arginine, but not by D-arginine. This suggests that the analgesic effect of acetaminophen is related to inhibition of NO generation. Potential mechanisms for this may involve NMDA and SP. Our data suggest that a significant portion of the analgesic effect of acetaminophen, when used clinically, may be related to an interaction with the central nervous system L-arginine-NO pathway.
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PMID:Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P. 752 8

Endothelium derived relaxing factor (EDRF), now widely believed to be nitric oxide (NO), may play an important part in the control of fetoplacental vascular tone. To further explore this role we have determined the relaxation responses to exogenous NO and examined the temporal relationship between intracellular concentrations of cyclic GMP and vascular tone in isolated ring segments of human chorionic plate arteries. We have also determined the dose relations for the contractile agonists serotonin and the thromboxane analog U46619. Lastly, we have explored the relaxation responses to a wide range of agents known to elicit EDRF release in other vascular beds. Chorionic plate arteries relaxed significantly to exogenous NO with concomitant increases in cyclic guanosine monophosphate over basal values. ED50s for serotonin and U46619 were 1.48 x 10(-6) M and 3.39 x 10(-8) M respectively. The ED50 for NO derived from S-nitroso-N-acetyl-penicillamine was 1.28 x 10(-6) M. Endothelium-intact segments of chorionic plate arteries pre-contracted with either serotonin or U46619 failed to relax significantly to acetylcholine, adenosine diphosphate, A23187, bradykinin, and histamine and only minimally to substance P. We suggest that EDRF is likely to be important in the control of placental vascular tone, but that it is not possible to demonstrate its action in an unperfused experimental system.
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PMID:Endothelium-derived relaxing factor and cyclic GMP-dependent vasorelaxation in human chorionic plate arteries. 752 60

1. The site of action at which nitric oxide (NO) may contribute to neurogenic vasodilatation in the hindpaw skin of urethane-anaesthetized rats was examined by the use of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. 2. Skin blood flow was measured by laser Doppler flowmetry, and neurogenic vasodilatation was evoked either by topical application of mustard oil (5%) or antidromic electrical stimulation of the saphenous nerve (antidromic vasodilatation). 3. L-NAME (60 mumol kg-1, i.v.) attenuated the hyperaemia evoked by mustard oil in an enantiomer-specific manner but failed to reduce antidromic vasodilatation and the vasodilatation due to i.v. injected calcitonin gene-related peptide (CGRP) and substance P (0.1-1 nmol kg-1 each), two proposed mediators of neurogenic vasodilatation. 4. Pretreatment of rats with capsaicin (125 mg kg-1, s.c. 2 weeks beforehand), to defunctionalize afferent neurones, reduced the hyperaemic response to mustard oil and prevented L-NAME from further decreasing the vasodilatation evoked by mustard oil. 5. Intraplantar infusion of sodium nitroprusside (SNP, 0.15 nmol in 1 min), a donor of NO, induced hyperaemia which was significantly diminished by the CGRP antagonist CGRP8-37 (50 nmol kg-1, i.v.) and by capsaicin pretreatment. The ability of CGRP8-37 to inhibit the vasodilator response to SNP was lost in capsaicin-pretreated rats. 6. Taken together, these data indicate that NO does not play a vasorelaxant messenger role in neurogenic vasodilatation but can contribute to activation of, and/or transmitter release from, afferent nerve fibres in response to irritant chemicals.
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PMID:Cutaneous vasodilatation induced by nitric oxide-evoked stimulation of afferent nerves in the rat. 752 93

Neuronal plasticity associated with altered sensations arising from tissue damage involves both established (e.g. substance P and excitatory amino acids) and novel (e.g. nitric oxide and metabolites of arachidonic acid) mediators released from terminals of primary afferent neurons or synthesised in the spinal cord. These and other mediators lead to activity-dependent synaptic plasticity and enhanced sensitivity to noxious stimuli (hyperalgesia). Activation of the N-methyl-D-aspartate (NMDA) receptor results in a calcium-dependent production of nitric oxide, while activation of alpha-amino-3-hydroxy-5-methylisoxazole-5-propionate (AMPA)-and 1,3- trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD)-sensitive glutamate receptors results in a phospholipase A2 (PLA2)-mediated production of different intracellular mediators, including arachidonic acid. Thermal hyperalgesia requires NMDA receptor activation and is primarily mediated by production of nitric oxide. Mechanical hyperalgesia requires AMPA and metabotropic glutamate receptor coactivation, and is primarily mediated by cyclo-oxygenase products of arachidonic acid metabolism.
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PMID:Spinal mediators of hyperalgesia. 752 81

We evaluated the effects of nitric oxide (NO) generators and endogenous production of NO elicited by substance P (SP) in the angiogenesis process. Angiogenesis was monitored in the rabbit cornea in vivo and in vitro by measuring the growth and migration of endothelial cells isolated from coronary postcapillary venules. The angiogenesis promoted in the rabbit cornea by [Sar9]-SP-sulfone, a stable and selective agonist for the tachykinin NK1 receptor, and by prostaglandin E1 (PGE1), was potentiated by sodium nitroprusside (SNP). Conversely, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), given systemically, inhibited angiogenesis elicited by [Sar9]-SP-sulfone and by PGE1. Endothelial cells exposed to SNP exhibited an increase in thymidine incorporation and in total cell number. Exposure of the cells to NO generating drugs, such as SNP, isosorbide dinitrate, and glyceryl trinitrate, produced a dose-dependent increase in endothelial cell migration. Capillary endothelial cell proliferation and migration produced by SP were abolished by pretreatment with the NO synthase inhibitors N omega-mono-methyl-L-arginine (L-NMMA), N omega-nitro-L-arginine (L-NNA), and L-NAME. Exposure of the cells to SP activated the calcium-dependent NO synthase. Angiogenesis and endothelial cell growth and migration induced by basic fibroblast growth factor were not affected by NO synthase inhibitors. These data indicate that NO production induced by vasoactive agents, such as SP, functions as an autocrine regulator of the microvascular events necessary for neovascularization and mediates angiogenesis.
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PMID:Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. 752 53

The purpose of this study was to determine the effects of tachykinins on prostanoid production by the dog ileum and to characterize the tachykinin receptor(s) responsible for the principal eicosanoid shown to be released, 6-keto-PGF1 alpha. Substance P, the selective NK1 receptor agonist [Sar9,Met(O2)11]substance P and neurokinin A caused concentration-dependent production of 6-keto-PGF1 alpha; neurokinin A was least potent. The selective NK2 agonist [Nle10]neurokinin A(4-10) had no effect. The selective NK1 antagonist CP-96,345 (10(-7) M), blocked 6-keto-PGF1 alpha release from substance P (10(-7) M), [Sar9,Met(O2)11]substance P (10(-7) M) and neurokinin A (10(-7) M). Although the putative NK2 antagonist MEN 10207 (10(-7) M) partially blocked the 6-keto-PGF1 alpha release induced by neurokinin A (10(-7) M), we conclude that all these peptides acted primarily on NK1 receptors to induce 6-keto-PGF1 alpha. Additional experiments suggest that a major site of production of 6-keto-PGF1 alpha in the canine ileum may be the vasculature, but these experiments do not exclude other sources such as intestinal muscle for this prostanoid. Calcium-free Krebs' solution partially reduced the release of 6-keto-PGF1 alpha to substance P (10(-7) M), implying that extracellular calcium helps support tachykinin-induced production of 6-keto-PGF1 alpha. Blockade of synthesis of another vasoactive mediator, endothelium-derived relaxing factor (nitric oxide), by N omega-L-arginine methyl ester) did not alter substance P-induced release of 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NK1 receptors mediated release of 6-keto-PGF1 alpha from the ex vivo perfused canine ileum. 752 25

We studied effects of nicotinic, muscarinic, serotoninergic, dopaminergic, adrenergic, vasoactive intestinal peptide (VIP) antagonists, VIP, nitric oxide-synthase inhibitors and stimulators alone and in combination with tetrodotoxin on substance P (SP)-stimulated intraluminal tone of the isolated proximal, middle and distal rat colon. Tetrodotoxin significantly enhanced SP-stimulated intraluminal tonic pressure in the distal, but not in the middle and proximal colon. N omega-nitro-L-arginine methylester enhanced SP stimulation in all colonic segments, whereas L-arginine inhibited it partially and D-arginine did not affect it. Atropine and hexamethonium partially inhibited SP stimulation of the middle and distal colon. Tetrodotoxin completely abolished the effects of L-arginine, atropine and/or hexamethonium on SP stimulation. Propranolol, phentolamine, reserpine, telenzepine, naloxone, Mr 2266, a VIP antagonist (H9935) and ketanserin did not affect SP-induced colonic muscle stimulation. VIP strongly reduced SP-stimulated intraluminal pressure in all colonic segments. VIP(10-28), a putative VIP antagonist, produced similar inhibition of SP-stimulated intraluminal tonic pressure, but did not affect N omega-nitro-L-arginine methylester-induced enhancement of SP-stimulated intraluminal pressure in any segments. It is concluded that in the isolated rat colon SP-stimulated intraluminal pressure (mainly generated by circular muscles) by a direct action on colonic muscles over the whole colonic length and by simultaneous activation of neural cholinergic excitatory pathways in the middle and distal, of noncholinergic excitatory pathways in the proximal colonic segment, and by activation of nitric oxide-dependent inhibitory neural pathways. VIP seems not to be directly involved in this inhibitory pathway.
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PMID:Substance P activates rat colonic motility via excitatory and inhibitory neural pathways and direct action on muscles. 752 33

Nitric oxide (NO) modulates myocardial contractile behavior in several isolated preparations, e.g., cardiac myocytes and papillary muscles, via elevation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We have recently reported that the exogenous NO donor, sodium nitroprusside, selectively modulates left ventricular (LV) relaxation in the isolated ejecting guinea pig heart, independent of coronary flow. We now report the effects of endogenously released NO on LV performance in this preparation (constant heart rate and loading). Both bradykinin (1 nM, n = 6) and substance P (100 nM, n = 6) accelerated early LV relaxation (maximum change in time constant, tE, -10.5 +/- 1.6 and -13.4 +/- 2.1%, respectively; both P < 0.05), without significantly altering early systolic parameters (e.g., rate of LV pressure development). These effects were inhibited by hemoglobin (P < 0.05; n > or = 6), which inactivates NO. Bradykinin (100 nM, n = 10) had an additional negative inotropic effect, which was not inhibited by hemoglobin. Neither agonist altered relaxation in isolated papillary muscles. These data suggest that endogenous NO, probably released from coronary microvascular endothelial cells, modulates LV relaxation in the intact heart.
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PMID:Modulation of left ventricular relaxation in isolated ejecting heart by endogenous nitric oxide. 752 13

The contribution of the intracellular messengers nitric oxide, arachidonic acid and protein kinase C to persistent nociception in response to tissue injury in rats was examined following the subcutaneous injection of formalin into the hindpaw. Formalin injury-induced nociceptive behaviours were reduced by intrathecal pretreatment with inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester, L-NAME), arachidonic acid (dexamethasone) or protein kinase C [protein kinase C (19-26) and 1-95-(isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride, H-7]. Each of these agents affected the tonic, but not the acute, phase of the formalin response. Furthermore, none of these agents affected mechanical or thermal flexion reflex thresholds in rats not injected with formalin. Conversely, formalin-induced nociceptive responses were enhanced by stimulators of nitric oxide (sodium nitroprusside), arachidonic acid metabolism (arachidonic acid) or protein kinase C [(+/-)-1-oleoyl-2-acetyl-glycerol], and were slightly reduced by inositol trisphosphate. Mechanical flexion reflexes were also reduced by arachidonic acid, while thermal flexion reflexes were reduced after treatment with sodium nitroprusside, arachidonic acid or [(+/-)-1-oleoyl-2-acetyl-glycerol]. The enhancement of formalin nociceptive behaviours (hyperalgesia) in rats treated with L-glutamate or substance P was reversed by pretreatment with inhibitors of nitric oxide (L-NAME), arachidonic acid (dexamethasone) or protein kinase C (H-7). The results suggest that central sensitization and persistent nociception following formalin-induced tissue injury, and the hyperalgesia in the formalin test induced by L-glutamate and substance P, are dependent on the intracellular messengers nitric oxide, arachidonic acid and protein kinase C.
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PMID:Intracellular messengers contributing to persistent nociception and hyperalgesia induced by L-glutamate and substance P in the rat formalin pain model. 752 41


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