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)

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators.
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PMID:Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig. 172 66

Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10(-8) M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.
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PMID:Acute effect of substance P in immunologic vasculitis in the rat colon. 172 22

Tracheas from control rats or rats sensitized to egg albumin (EA) were studied in vitro in Ussing chambers, and changes in short-circuit current (Isc) induced by the addition of antigen or agonists on the mucosal (luminal) side were recorded. Addition of EA (100 micrograms/ml) to tracheas from sensitized but not from control rats caused a slow increase of Isc beginning after 15 to 30 s and maximal at 3 to 4 min. This response was inhibited in the presence of doxantrazole, a mucosal mast-cell-stabilizing agent, but not by sodium cromoglycate. A separate group of rats was treated neonatally with capsaicin to deplete peptide neurotransmitters. Responses to EA were significantly lower in capsaicin-treated, sensitized rats than in untreated, sensitized control littermates. No difference was seen in the level of serum EA-specific IgE in these two groups. In tracheas from untreated rats, addition of substance P, capsaicin, platelet-activating factor, and acetylcholine caused an immediate and marked increase in Isc. Responses to substance P and acetylcholine were unaffected by capsaicin treatment. However, responses to capsaicin itself and also to PAF were reduced. These data indicate that changes of net ion transport across the airway epithelium are early phenomena of local hypersensitivity reactions, and that neurotransmitters such as substance P may play an important role in the control of these phenomena.
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PMID:Ion transport in rat tracheal epithelium in vitro. Role of capsaicin-sensitive nerves in allergic reactions. 196 24

1. We describe the actions of GR43175, a 5-hydroxytryptamine1 (5-HT1)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2. GR43175 markedly attenuated extravasation of 125I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 micrograms kg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, P less than 0.005). 3. GR43175 (100 micrograms kg-1, i.v., rats; 30 micrograms kg-1, guinea-pigs) decreased the leakage of radiolabelled albumin from 163% to 119% (P less than 0.005, guinea-pig) or from 174 to 118% (P less than 0.05, rat) above vehicle-treated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 mumol kg-1, i.v.). 4. GR43175 (30-300 micrograms kg-1) did not block plasma protein extravasation within extracranial tissues of rats and guinea-pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip). 5. The protein leakage which followed the i.v. administration of 5-HT (1 mumol kg-1) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg-1 or 1 nmol kg-1) and neurokinin A (1 nmol kg-1), was not blocked by GR43175 (100, 300 micrograms kg-1) despite the presence of leakage in amounts equivalent to that following neurogenic stimulation. 6. GR43175 (100 micrograms kg-1) decreased bradykinin (10 mumol kg-1)-induced extravasation from 142 to 115% above vehicle-treated animals (P less than 0.05). 7. These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.
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PMID:The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. 215 35

In the guinea-pig isolated, perfused lung, the effect of albumin on oedema formation and bronchoconstriction as well as on capsaicin-induced overflow of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity has been examined. CGRP was used as an indicator of sensory nerve activation since it is more stable than the tachykinins substance P and neurokinin A. As expected, the lung water content was significantly (P less than 0.001) higher in lungs perfused with albumin-free buffer than when the buffer contained 4.5% albumin. Also, in albumin-free buffer the baseline airway resistance (RL) was increased and dynamic compliance (CDYN) reduced (P less than 0.001). Capsaicin (1 x 10(-6) M) was about 100 times less potent as a bronchoconstrictor when preincubated with albumin for 45 min, and the associated overflow of CGRP-LI was inhibited (from 221.0 +/- 63.4 fmol to 8 fmol fraction-1). When CGRP (50-200 pM) was incubated for 60 min with albumin, the recovery of CGRP-LI was 48% lower (P less than 0.01) than in the absence of albumin, corresponding to a loss rate of about 1% min-1. Catabolism or binding of neuropeptides can therefore hardly explain the diminished bronchoconstrictor potency of capsaicin. Capsaicin was also less effective as a constrictor in isolated bronchi after preincubation with albumin, suggesting that capsaicin itself may be bound or absorbed to this macromolecule. The bronchoconstrictor response to adenosine was also diminished in the presence of albumin. Adenosine was about 1000 times less potent as a bronchoconstrictor if dissolved in albumin 45 min before infusion, but only 10 times less potent when administered as bolus doses to albumin buffer-perfused lungs. Metabolism of adenosine may be the reason for the decreased potency of adenosine. The enzymatic activity may have been associated with impurities in the albumin preparation used (bovine serum albumin fraction V is greater than or equal to 96% pure) or contained in the protein itself. Since the bronchoconstrictor effect of acetylcholine was not reduced in the presence of albumin, it is not likely that albumin affects directly the contractility of the smooth muscle. These data demonstrate the importance of studying the influence of albumin on the in-vitro actions of pharmacological agents. The absence or presence of albumin products in nutrient buffer solutions may mean dramatic differences in potencies of certain drugs. Furthermore, bolus injections of agents are preferable, and preincubation together with albumin should be avoided.
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PMID:Albumin protects against capsaicin- and adenosine-induced bronchoconstriction and reduces overflow of calcitonin gene-related peptide from guinea-pig lung. 219 39

This study examined the electrophysiological responses to antigen and to various stimuli in jejunal mucosa from rats sensitized to egg albumin with alum and pertussis adjuvants. Luminal antigen caused an immediate increase in short-circuit current, a measure of net ion transport, which was one of three different patterns. All were inhibited by the chloride channel blocker diphenyl-2-carboxylate, by chloride-free buffer, and by doxantrazole, a mast cell stabilizer. Depending on the pattern, the histamine-1 antagonist diphenhydramine, the 5-hydroxytryptamine-2 antagonist ketanserin, and the cyclooxygenase inhibitor piroxicam also reduced the responses. A neural component was indicated by inhibition of the responses to luminal antigen by the neurotoxin tetrodotoxin and by neonatal capsaicin treatment, which depletes substance P-containing nerves. In the absence of antigen, histamine and substance P caused increases in short-circuit current; the magnitude of these changes was significantly greater in tissues from sensitized animals than in controls. These data suggest that sensitization itself may result in hypersecretory responses to some inflammatory mediator and neurotransmitter substances.
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PMID:Allergic reactions of rat jejunal mucosa. Ion transport responses to luminal antigen and inflammatory mediators. 234 44

We examined the effects of the neuropeptide substance P on pulmonary hemodynamic and transvascular fluid filtration in isolated Ringer's-perfused and blood-enriched Ringer's-perfused guinea pig lung and on albumin flux across bovine pulmonary artery endothelial monolayer. Mean pulmonary artery, left atrial, and capillary pressures were determined and used to calculate arterial and venous resistances, and lung weight was continuously monitored. Substance P (0.01-1.0 microM) caused marked increases in pulmonary arterial pressure, capillary pressure, venous resistance, and lung weight within 3-5 minutes after administration. These responses remained elevated above baseline at the end of the 30-minute experimental period in the Ringer's-perfused lungs but not in the blood-enriched Ringer's-perfused lungs. Substance P did not alter the capillary filtration coefficient in isolated lungs and transendothelial albumin permeability in the endothelial monolayer. Substance P resulted in an increase in venous effluent thromboxane B2 concentrations in perfused lungs but had no effect on 6-keto-prostaglandin F1 alpha concentrations. Papaverine (0.27 mM) (a smooth-muscle relaxant) abolished the pulmonary microvascular response to substance P in Ringer's-perfused lungs, and meclofenamate (0.15 mM) (a cyclooxygenase inhibitor) attenuated the pulmonary vasoconstriction and lung weight increase. Pyrilamine (1.0 microM) (a histamine1-receptor antagonist) did not alter the responses to substance P. In conclusion, substance P does not affect pulmonary vascular permeability to water and protein. Substance P induces an intense pulmonary vasoconstriction (due to greater constriction of postcapillary vessels) and an elevation in pulmonary capillary pressure that increases net transvascular fluid filtration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P-induced pulmonary vasoreactivity in isolated perfused guinea pig lung. 244 56

An intravascular injection of substance P is known to increase vascular permeability in the rat trachea. Electrical stimulation of the cervical vagus nerve produces a similar response, presumably by releasing substance P or other tachykinins from sensory nerve endings. In the present study, we sought to determine whether the increase in vascular permeability induced by intravascular substance P or by vagal stimulation requires the presence of neutrophils or other components of circulating blood. To eliminate circulating blood, we perfused into the aorta of anesthetized rats an oxygenated Krebs-Henseleit solution containing albumin and monastral blue, a colloidal pigment that does not cross normal tracheal blood vessels. We then injected substance P intravascularly or electrically stimulated the right cervical vagus nerve. Increases in vascular permeability were quantified by using a microspectophotometer to measure the amount of extravasated monastral blue in tracheal whole-mounts. We found that the elimination of neutrophils and other components of circulating blood did not prevent the increase in tracheal vascular permeability induced by intravascular substance P or by vagal stimulation.
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PMID:Substance P-induced increase in vascular permeability in the rat trachea does not depend on neutrophils or other components of circulating blood. 246 55

The actions of serotonin and substance P have been examined with use of an isolated, vascularly perfused rabbit ileal preparation. The vascular perfusate was composed of a modified Krebs' buffer solution that contained washed human red blood cells (hematocrit, 15% to 20%) and 3% albumin, with no added hormones or peptides. Ileal blood flow was held constant at 49.3 +/- 3.1 ml/min per 100 gm wet weight of intestine. Net intestinal water and electrolyte fluxes were calculated by means of an isosmotic buffer that contained carbon-14 polyethylene glycol as a nonabsorbable volume marker. Viability of this isolated perfused ileal preparation was confirmed on the basis of light microscopy, oxygen consumption, and transmucosal potential difference measurements. Control experiments, without exogenous hormone infusion, resulted in a stable preparation with a basal secretory state. Intra-arterial serotonin at 2.5 micrograms/min (n = 10) significantly stimulated secretion of H2O, Na+, and Cl- (p less than 0.01). Intra-arterial substance P at 2.5 x 10(-1) micrograms/min (n = 7) significantly increased the secretion of H2O, Na+, and Cl- (p less than 0.02). The dose of serotonin was designed to yield serotonin levels that resembled those found circulating in patients with carcinoid syndrome. These data indicate that serotonin and substance P are potent secretagogues in a mammalian system, independent of their effect on mesenteric blood flow and in the absence of extra-intestinal hormonal and neural influences.
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PMID:Serotonin and substance P stimulate intestinal secretion in the isolated perfused ileum. 246 83

The irritation response of the rabbit eye to trigeminal nerve stimulation, which includes a breakdown of the blood-aqueous barrier (BAB), seems to be due to the release of substance P (SP) and calcitonin gene-related peptide (CGRP). In order to assess the relative importance of these two peptides for the barrier effect, and the role of arachidonic acid metabolites (AAM) in the response, we have studied the effects of intravenous injections of the peptides on the permeability of the blood vessels of the anterior uvea and the BAB using labelled albumins. At a dose of 120 pmol kg-1 there was marked leakage of labelled albumin into the aqueous humour in animals under pentobarbital anaesthesia. The leakage was enhanced by sympathotomy. In conscious animals 5 pmol kg-1 CGRP caused enhanced leakage from the blood vessels of the ciliary processes in those pre-treated with biperiden in order to abolish the cholinergic vasoconstrictor tone in the anterior uvea. 24 and 120 pmol kg-1 CGRP caused marked leakage of albumin and a breakdown of the epithelial part of the BAB. These effects were not modified by biperiden pre-treatment, but markedly reduced by pre-treatment with indomethacin. The protecting effect of indomethacin was lost when biperiden was given as well. SP did not cause a leakage with 5 nmol kg-1 and only moderate leakage with 25 nmol kg-1. This effect was abolished by pre-treatment with indomethacin but not if indomethacin was combined with biperiden.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intravenous calcitonin gene-related peptide (CGRP) and substance P on the blood-aqueous barrier in the rabbit. 246 20


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