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)

1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors.
 ...
PMID:Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor. 248 1

Classical techniques for studying modulations of microvascular permeability have a time resolution of minutes. A newly developed method allows continuous measurement of the electrical resistance of the microvascular membrane in vivo (Olesen & Crone 1983). The technique exploits microelectrodes impaled into the vascular lumen and is based on cable analysis of the vessel. It was applied to venules on the surface of the frog brain to test the effect on microvascular permeability of a wide variety of substances. The following agents increased ionic permeability reversibly within seconds: 5-hydroxytryptamine, bradykinin, ATP, ADP, AMP, phospholipase A2, arachidonic acid, leukotriene C4, oxygen-derived free radicals, ionophore A23187, and unbound Evans blue dye. An irreversible permeability increase was induced by protamine sulphate, neuraminidase, trypsin, melittin, and snake venoms from Crotalus durissus terrificus and Bothrops atrox. The following substances were without effect within an administration period of 5 min: histamine, epinephrine, putrescine, angiotensin II, vasoactive intestinal polypeptide (VIP), substance P, neurotensin, vasopressin, adenosine, PGE2, PGF2 alpha, prostacyclin (PGI2), leukotriene B4, albumin, heparin, plant cytokinins, hyaluronidase, thrombin, wasp venom. Variations in pH between 5.1 and 8.6 did not change permeability. Three conclusions are drawn from the observations: (1) the permeability of cerebral microvessels can be modulated by specific agents, (2) the agents induced changes in the endothelium within a few seconds, and (3) the rapid permeability increase induced by inflammatory mediators was less than two-fold and reversible within minutes.
 ...
PMID:Substances that rapidly augment ionic conductance of endothelium in cerebral venules. 348 16

A sensitive and specific RIA system has been developed for measuring somatostatin (SRIF) in plasma. On chromatographic analysis of the plasma of portal blood of rats, two peaks of SRIF-like immunoreactivity were found, one (large form) near the position of albumin and the other (small form) in the same position as synthetic SRIF. The nature of the large form is unknown, but the small form was immunologically and physicochemically indistinguishable from synthetic cyclized SRIF. After iv injection of substance P (10 micrograms/100 g BW) into rats, there was a significant increase in the portal plasma level of SRIF from the basal values of 277 +/- 75 to 1130 +/- 111 pg/ml at 15 min. On the other hand, the pancreatic SRIF concentration decreased from 0.27 +/- 0.01 to 0.16 +/- 0.04 ng/mg wet wt at 15 min and was maintained at a low level up to 30 min after the injection. Injection of substance P did not affect the SRIF concentration in the stomach. Similar results were obtained after iv administration of neurotensin (3 micrograms/100 g BW). These findings suggest that increases in the portal plasma levels of SRIF in rats treated with substance P or neurotensin may reflect, at least in part, the release of SRIF from the pancreas. The physiological significance of SRIF secretion remains to be clarified, but this study suggests that SRIF can be released from the digestive organs, including the pancreas, into the portal vein and may act on the tissues in the peripheral area.
 ...
PMID:Effects of substance P and neurotensin on somatostatin levels in rat portal plasma. 615 2

Substance P (SP), a putative neuropeptide transmitter, was examined for its effects on macrophages. Guinea-pig peritoneal macrophages were purified by adherence, challenged with SP and incubated for up to 18 h. Culture supernatants were collected to determine the release of O-2, H2O2 and TXB2. SP dose-dependently evoked O-2 and H2O2 production by C. parvum-activated macrophages and liberation of TXB2 from albumin-elicited macrophages. Generation of these proinflammatory macrophage products by SP may be relevant in the context of neuroinflammatory disease.
 ...
PMID:Activation of macrophages by substance P: induction of oxidative burst and thromboxane release. 619 98

Topical glucocorticoid treatment (betamethasone-17-valerate (0.018 mg/cm2, 3 h pretreatment) significantly inhibited neurogenic oedema formation induced by electrical antidromic stimulation (2 Hz, 15 V, 0.1 ms for 5 min) of the rat saphenous nerve; a response mediated by neuropeptides released from activated capsaicin-sensitive sensory C-fibres. Oedema formation was estimated by measurement of extravasation of i.v. injected 125I-albumin into skin. The inhibitory effect of the topical glucocorticoid was reversed by passive immunisation of rats with polyclonal antibody to the glucocorticoid-inducible anti-inflammatory protein lipocortin 1 (1 ml/kg, s.c., 24 h pretreatment) whilst a non-immune serum was without effect. Similarly the glucocorticoid receptor antagonist RU38486 (20 mg/kg, 2 and 20 h pretreatment) abrogated the response indicating specific binding to glucocorticoid receptors. Topical glucocorticoid treatment also inhibited the oedema produced by intradermal substance P (0.1 nmol) in the dorsal skin of rats. Topical glucocorticoid inhibited neurogenic oedema formation partly through a mechanism dependent upon lipocortin 1. This inhibition may be partly due to a post-junctional effect upon substance P activity/binding however a pre-junctional component cannot be excluded.
 ...
PMID:Topical glucocorticoids inhibit neurogenic inflammation: involvement of lipocortin 1. 749 10

The hypothesis that the endothelium-derived relaxing factor/nitric oxide (EDNO) activity is elevated in chronic hypoxic pulmonary hypertension (CH-PHT) was tested using isolated Krebs-albumin-perfused rat lungs. Concentration of the EDNO decomposition products (NOx) in the lungs' effluent was measured by a modified chemiluminescence assay. The functional significance of basal EDNO production was studied by measuring the vasoconstrictor response to an EDNO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Reactivity to the endothelium-dependent vasodilator substance P and to exogenous NO was also studied. More NOx was found in effluent from CH-PHT (22.3 +/- 9.8 nM) than control (0.4 +/- 3.9 nM) lungs. The L-NAME-induced vasoconstriction was greater in CH-PHT than in control rats. The sensitivity, but not the maximal vasodilation, to exogenous NO was elevated in CH-PHT. The substance P-induced vasodilation was potentiated in CH-PHT compared with control rats and blocked by L-NAME in both groups. We conclude that basal and agonist-stimulated pulmonary EDNO activity is enhanced in this model of CH-PHT. The EDNO synthesis may play a counterregulatory role in CH-PHT.
 ...
PMID:Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats. 751 87

Trigeminal sensory nerves release neurotransmitters such as calcitonin gene-related peptide (CGRP), substance P, and others in human nasal mucosa. The effects of CGRP on nasal secretion were tested in humans in vivo by applying CGRP directly to nasal mucosa and then lavaging the nostrils ten minutes later. Concentrations of total protein, albumin, lysozyme, and orcinol-reactive mucoglycoconjugates were measured in lavage fluid. Calcitonin gene-related peptide (0.1 to 100 micrograms) did not stimulate secretion of any of these markers indicating that CGRP had no effect on glandular secretion or albumin exudation in vivo. These findings indicate that CGRP did not stimulate glands or endothelial cells of the vessels that regulate plasma extravasation. These data are consistent with previous studies that demonstrate 125I-CGRP binding sites on arterial vessels without detecting sites on glands or epithelium, the absence of effects of CGRP on glandular secretion from human nasal mucosal explants in vitro, and the apparently minor magnitude of sensory nerve axon responses in humans in vivo.
 ...
PMID:Calcitonin gene-related peptide nasal provocation in humans. 751 5

Mammalian ventral roots and pia mater contain sensory C-fibers, some of which exhibit a substance P- and/or calcitonin gene-related peptide (CGRP)-like immunoreactivity. At some locations, sensory axons containing these neuropeptides evoke peripheral plasma protein extravasation after antidromic electrical stimulation. Such axons usually disappear following treatment of neonatal rats with capsaicin. The purpose of the present study is to find out if afferent C-fibers in the rat ventral roots L4 and L5 are capsaicin-sensitive, and if antidromic stimulation of these fibers elicits extravasation in the root and/or the ventral pia mater. The results show (1) that the number of C-fibers in these ventral roots is unaffected by neonatal capsaicin treatment, as seen in the electron microscope; (2) that the occurrence and general configuration of axons with substance P- and CGRP-like immunoreactivity do not appear abnormal in neonatally capsaicin-treated rats, as revealed by fluorescence microscopy on longitudinal frozen sections; (3) that Evans blue albumin is not extravasated in the ventral root or pia mater after electrical ventral root stimulation or following systemic injection of capsaicin. We conclude, that ventral root afferents are functionally different from otherwise similar afferents at other locations.
 ...
PMID:Sensory C-fibers in rat ventral roots are capsaicin-insensitive and they do not mediate extravasation from pial vessels. 751 24

The effects of intravenous injection of prostaglandin E2 (PGE2), substance P (SP) and a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]-SP (5-11) on plasma extravasation of albumin in the rat after blockade of prostaglandin synthesis with indomethacin or chemical sympathectomy with guanethidine were studied. Blood pressure was decreased by all agonists, but only the hypotensive effects of SP were enhanced by pretreatment with indomethacin and guanethidine. The increase in plasma extravasation induced by PGE2 in the tongue, skin and lungs was blocked by both guanethidine and indomethacin. Pretreatment of the rats with guanethidine or indomethacin increased extravasation induced by SP in the tongue-tip, dorsal skin and foot, but decreased the enhanced permeability in the pinna, and did not alter the actions of the peptide in other tissues. In contrast, both guanethidine and indomethacin pretreatment increased vascular permeability responses to [pGlu5,Me-Phe8,Sar9]-SP (5-11) administration in 9 and 14 of 16 tissues examined, respectively. Thus, intact sympathetic nerves and functional cycloxygenase activity exert inhibitory constraints on the vascular permeability effects of intravenously administered SP or its analogue. On the other hand the integrity of the sympathetic nerves and prostaglandin synthesis are required for PGE2-induced increases in vascular leak.
 ...
PMID:The involvement of sympathetic nerves in plasma extravasation induced by prostaglandin E2 and substance P. 751 25

The effect of the neurokinin-1 (NK1) receptor antagonist RP67580 in modulating inflammatory oedema formation has been investigated in guinea-pig skin. Oedema formation was measured over 30 min by the extravascular accumulation of intravenously-injected 125I-albumin in the anaesthetised guinea-pig. RP67580 was injected intradermally with the agents under test. Intradermal RP67580 (10 nmol/site) inhibits oedema formation induced by substance P (30 pmol) and neurokinin A (100 pmol), but not that induced by bradykinin (10-1000 pmol) or histamine (10 nmol). Substance P-induced oedema formation is similar in control (saline) and mepyramine (histamine H1 receptor antagonist) pretreated guinea-pigs suggesting a minimal involvement of histamine in substance P induced oedema formation in guinea-pig skin. Oedema formation induced by intradermal carrageenin (0.2%) was not inhibited by RP67580 (1-10 nmol). A significant but partial inhibition of oedema formation induced in a passive cutaneous anaphylaxis (PCA) response was observed. The oedema formation in the PCA was inhibited 50% by mepyramine pretreatment but in the presence of mepyramine no further inhibition of the PCA response by RP67580 was observed.
 ...
PMID:Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by tachykinins, carrageenin and an allergic response in guinea-pig skin. 752 80


<< Previous 1 2 3 4 5 6 7 8 9 Next >>