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)

To study the effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage, we measured concomitant changes in lung resistance (RL) and in extravasation of Evans Blue dye in the airways of anesthetized immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). RL was measured for 6 min after iv. histamine (0, 5, 15, 30 and 50 micrograms/kg). For comparison, responses after 1 microgram/kg substance P were also examined. After measurement of RL, microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was also examined in the same animal. Immature animals required a larger dose of histamine than adults to achieve a similar degree of maximal bronchoconstriction after histamine. In contrast, equal doses of histamine (15 and 30 micrograms/kg) induced a significantly greater extravasation of dye in immature airways in both proximal and distal intrapulmonary airways, although not in trachea or main bronchi. Substance P did not cause any age-related differences in dye extravasation at any airway level. These results suggest that i.v. histamine specifically causes a greater degree of airway microvascular leakage in peripheral airways but induces less smooth muscle contraction in the airways of immature guinea pigs than in the airways of adult animals.
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PMID:Effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage in guinea pig airways. 138 18

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.
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PMID:Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema. 170 92

The effect of intradermal injection of Spantide II, a novel tachykinin antagonist, and the neuropeptide galanin on neurogenic plasma extravasation induced by antidromic stimulation of C-fibers in the sciatic nerve was examined in the hindpaws of rats. Activation of C-fibers by antidromic sciatic nerve stimulation (2 Hz, 5 min) consistently evoked a localized plasma extravasation of Evans Blue in the skin area of the hindpaw innervated by the sciatic nerve. Intradermal injection of 3 nmol Spantide II significantly inhibited this response. The plasma extravasation was nearly totally abolished when the concentration of Spantide II was increased to 9 nmol. Intradermal injection of 1.5 and 15 nmol galanin also inhibited plasma extravasation. Intradermal injection of 9 nmol Spantide II effectively blocked the plasma extravasion in the hindpaw induced by 8 nmol intravenous substance P. Plasma extravasation induced by intravenous substance P was also inhibited by the higher, but not by the lower, dose of galanin injected intradermally. The present results indicate that Spantide II, a potent non-toxic tachykinin antagonist, effectively blocks the neurogenic plasma extravasation induced by antidromic C-fiber stimulation, thus supporting the view that tachykinins play an important role in this neurogenic inflammatory process. It is further shown that galanin, a naturally occurring neuropeptide present in primary afferents, also inhibits C-fiber activation-evoked plasma extravasation, indicating an interaction between galanin and tachykinins in the peripheral terminals of primary afferents, possibly through both pre- and postsynaptic mechanisms.
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PMID:Spantide II, a novel tachykinin antagonist, and galanin inhibit plasma extravasation induced by antidromic C-fiber stimulation in rat hindpaw. 172 Feb 25

Local and systemic capsaicin pretreatment as well cryosurgery induced a long-lasting loss of sensory substance P-immunoreactive nerves in the guinea-pig nasal mucosa. In addition, cryosurgery caused a loss of noradrenergic sympathetic nerves, sclerosis of blood vessels, epithelial damage and fibrosis of the mucosa. The sneezing response to local application of capsaicin--but not that to nicotine--was reduced or abolished by capsaicin pretreatment and cryosurgery, while the response to tactile stimulation was unaffected. These effects were long-lasting and still present 2 months after treatment. Local capsaicin pretreatment of the nasal mucosa had no effects on the substance P levels or the Evans Blue extravasation response to i.v. capsaicin in the ureter, indicating that this treatment has no systemic effects on other afferent SP-neurons. It is suggested that local capsaicin pretreatment is a more selective and less traumatic method than cryosurgery to induce a long-lasting desensitization of the nasal mucosa to chemical irritants in hyperreactive disorders of the nose.
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PMID:Effects of nasal capsaicin pretreatment and cryosurgery on sneezing reflexes, neurogenic plasma extravasation, sensory and sympathetic neurons. 241 Oct 99

The release of tachykinins from isolated slice preparations of the guinea-pig spinal cord and ureter was studied in vitro. Capsaicin (10 microM) caused release of substance P, neurokinin A and an eledoisin-like component from both the spinal cord and ureter. The release of tachykinins induced by capsaicin or potassium (60 mM) was calcium dependent. No detectable release of neurokinin B or neuropeptide K, an N-terminally extended form of neurokinin A, was induced by capsaicin. No detectable release of tachykinins could be demonstrated after exposure to agents which are known to activate C-fibre afferents, such as histamine, bradykinin, serotonin, prostaglandins E1, E2 or acetylcholine. Protein extravasation in the ureter, as determined by the Evans Blue extravasation technique was used as a functional correlate to the tachykinin release. Protein extravasation was induced in vivo by local intraluminal injections of capsaicin at several hundred-fold lower concentrations than those required to induce a detectable release of tachykinins in vitro. The difference may, however, partly depend on the experimental conditions and the detection limit of the tachykinin assay used. The protein extravasation response to capsaicin was absent after systemic capsaicin pretreatment, which causes a marked depletion of tachykinins in the ureter. In conclusion, capsaicin evokes release of several tachykinins from both central and peripheral endings of primary afferent neurons. The peptides released from sensory nerves in the periphery may induce effects such as protein extravasation and smooth muscle contraction.
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PMID:Capsaicin induced release of multiple tachykinins (substance P, neurokinin A and eledoisin-like material) from guinea-pig spinal cord and ureter. 243 50

Immunohistochemistry combined with retrograde tracing has been used to show that of the afferent neurons supplying the dorsomedial surface of the hind paw, approximately 30% contain substance P and 50% calcitonin gene-related peptide immunoreactivity. Stimulation of the saphenous nerve causes plasma extravasation and antidromic vasodilatation in this area of skin. The roles of calcitonin gene-related peptide and substance P released from peripheral afferent endings in mediating these effects were examined using immunoneutralization. In pilot experiments, the binding of radiolabelled peptide to the immunoglobulin fraction of calcitonin gene-related peptide and substance P antisera was characterized in quasi-physiological conditions. Systemic administration of either substance P or calcitonin gene-related peptide antibodies caused a significant decrease (P less than 0.05) in plasma extravasation measured by the Evans Blue method in response to topical application of mustard oil (0.5%) to the skin, or of capsaicin (5 microM) to the saphenous nerve. Topical application of mustard oil also produced a 52.9 +/- 5.1% increase in skin red cell flux. This increase was significantly decreased by both substance P and calcitonin gene-related peptide antibodies. The results suggest that both peptides are involved in mediating neurogenic inflammatory responses.
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PMID:The role of substance P and calcitonin gene-related peptide in neurogenic plasma extravasation and vasodilatation in the rat. 248 Dec 41

We have studied quantitatively the levels of substance P and calcitonin gene-related peptide in nerves innervating skin and muscle of rats, and examined the effects of cross-anastomosing these nerves so that they regenerate to an inappropriate target. We have also compared the ability of nerves to induce neurogenic extravasation with their peptide content. Peptide was measured by radioimmunoassay in the proximal section of ligated peripheral nerves, and neurogenic oedema was measured by determination of Evans Blue extravasation induced by either systemic capsaicin treatment or topical mustard oil application. The levels of these peptides are higher in cutaneous nerves than muscle nerves. This cannot be explained by differences in the number of fibres in the nerves studied. The levels of peptides fall when cutaneous afferents reinnervate muscle, and rise when muscle afferents reinnervate skin. We suggest that these changes occur because of some tissue-specific trophic influence arising from the tissue innervated. The ability to produce extravasation in skin is highly correlated with the substance P and calcitonin gene-related peptide levels of its innervation, even when this occurs in inappropriate nerves which do not normally produce extravasation.
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PMID:Quantitative analysis of peptide levels and neurogenic extravasation following regeneration of afferents to appropriate and inappropriate targets. 248 Dec 46

The histology of blisters induced in rats using dry-ice or vacuum applied to the hind limb footpad has been examined by light microscopy and indirect fluorescence immunohistochemistry for substance P like immunoreactivity. The effects of sciatic nerve stimulation on plasma extravasation as determined by estimation of Evans Blue content of blister fluid has been examined. Plasma extravasation occurs in both blister types following nerve stimulation. Plasma extravasation may be induced by substance P released from nerve terminals in the blister wall. Vacuum induced blisters have less tissue and nerve damage and therefore less of an inflammatory response, but plasma extravasation is greater in thermal blisters. Blisters serve as a useful model for the study of neurogenic inflammation.
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PMID:Neurogenic inflammation in skin blisters. 402 11

Neuropeptides, including substance P (SP) may play a role in neurogenic inflammation. Although SP-immunoreactive (SP-IR) axons are known to be present within the oral mucosa (OM) and salivary glands, the functional significance of SP in oral mucosa and sublingual salivary gland (SLG) is not fully understood. The present experiments were carried out to study the effects of SP infused into the left common carotid artery on vascular permeability in the OM and in the SLG of male rats. Vascular permeability was assessed on the basis of Evans Blue extravasation. Separate groups of animals received histamine (H1) receptor antagonist (chloropyramine, 10 mg kg-1 i.v.) or prostaglandin synthesis inhibitor (indomethacin, 4 mg kg-1 i.v.) prior to SP infusions. Infusion of SP in doses of 30 and 74 pmol min-1 increased the vascular permeability of OM by 162.3 +/- 16.3% (n = 8, p < 0.05) and 482.7 +/- 46.7% (n = 8, p < 0.001), respectively. SP in a dose of 15 pmol min-1 did not increase Evans Blue extravasation in OM (38.3 +/- 4.0 micrograms g-1, n = 8, compared to the control: 44.0 +/- 7.9 micrograms g-1, n = 8, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of substance P administration on vascular permeability in the rat oral mucosa and sublingual gland. 747

Electrical stimulation of the distal stump of cut peripheral nerves is a commonly accepted way to evoke neurogenic inflammation. Nevertheless, the modulatory effect of biogenic amines and vasoactive peptides released from efferent fibres can be excluded only if the dorsal roots are stimulated. The present study was focussed to investigate plasma extravasation in the appropriate skin and mucosal areas as well as in the genito-urinary organs in response to antidromic stimulation of the lumbar and sacral dorsal roots of the rat. Plasma extravasation was detected by quantitative measurement of the accumulated Evans Blue tracer in tissue pieces. Two unilateral posterior roots were stimulated simultaneously (20 V, 0.5 ms, 5 Hz, 5 min) in each anaesthetized rat. Intensive blueing response occurred in the following tissues: plantar glabrous skin, L4-L5 (L6); dorsum of the hindpaw and ankle joint, L2-L4; ventral surface of the thigh, L2-L4 (L1); abdominal skin, L1-L4; caudal nipples, L1-L2; root of the tail, S1 orifice of the vagina, S1 (L6); vagina, L2-L3, L5-S1; cervix and corpus uteri, L2-L3, L5-S1; lower two-thirds of the uterine horns, L1-L3; urinary bladder, L1-L3, L6-S1; rectum, L5-S1; scrotum (dorsal surface and lower pole), L6-S1; scrotum (ventral surface), L3-L5. No significant dye accumulation was observed in the muscles, testicles, vas deferens and prostate. Plasma extravasation caused by antidromic activation of the dorsal roots was absent or highly reduced after systemic capsaicin pretreatment of the rats. Neurogenic inflammation evoked by antidromic stimulation of the dorsal roots makes this method suitable for mapping the organs where capsaicin-sensitive sensory nerve endings exert their "efferent functions". This first functional description of segmental innervation of capsaicin-sensitive afferent fibres is in agreement with retrograde tracing studies and immunohistochemical localization of substance P in the dorsal root ganglia and peripheral tissues.
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PMID:Plasma extravasation in the skin and pelvic organs evoked by antidromic stimulation of the lumbosacral dorsal roots of the rat. 747 70


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