<p>OBJECTIVETo explore the effect of substance P (SP) on the functional proteins on plasma membrane of neutrophil (Np).p><p>METHODThe response of Np to SP was examined by measuring the level of respiratory burst, the activities of ACP and ALP, the fluoroscopy intensity of CR3, CD45 and FM-LP.p><p>RESULTSIt was found that SP could increase respiratory burst of Np, decrease the activity of acid phosphatase (ACP), but had no effect on alkaline phosphatase (ALP). SP could also promote the amount of CD45, complement receptor type 3 (CR3) and N-Formyl-Met-Leu-Phe (FMLP) receptors.p><p>CONCLUSIONThe results showed that the effects of SP on functional proteins in human Np membrane were universality and diversity. It implied that SP could affect various inflammation responses in Np.p>
Acid Phosphatase ; metabolism ; Humans ; Membrane Proteins ; physiology ; Neutrophils ; metabolism ; Respiratory Burst ; Substance P ; pharmacology

<p>OBJECTIVETo investigate the influence of substance P (SP) on the release of histamine in the human hypertrophic scar tissue, and to explore the prerequisite of their interaction.p><p>METHODSTissue specimens of normal skin and hypertrophic scar from eight hospitalized patients were excised and cut into 0.5 to 1.0 mm3 pieces, and the histamine release by mast cell (MC) under the stimulation of different concentration of SP and calcium, as well as the different affect time of SP, were determined with fluorescence spectrometer. Then the histamine release rate was calculated.p><p>RESULTSThere was obvious release of histamine when SP concentration was 1 x 10(-6) mol/L , and the release rate was (50.0 +/- 3.6) %, which was significantly higher than that by SP in the concentration of 0 mol/L [(44.0 +/- 3.2) %, P < 0.01]. Therefore it seemed to be dose-dependent. About 90% of histamine was released within 15 minutes of 5 x 10(-1) mol/L Substance P stimulation, and it was also time-dependent. The histamine release reached the peak when calcium concentration was 5 x 10(-3) mol/L, which seemed to be dose-dependent, but it decreased transiently when calcium concentration was 1 x 10(-3) mol/L. In all occasions, the influence of SP on the histamine release by MC in hypertrophic scar (HS) was markedly higher than that in normal skin (NS) (P < 0.01). Conclusion The influence of SP on the histamine release by MC in HS was markedly higher than that in NS, and it might be closely related to itching sensation and the formation of hypertrophic scar.p>
Child ; Child, Preschool ; Cicatrix, Hypertrophic ; metabolism ; Female ; Histamine ; metabolism ; Humans ; Male ; Skin ; metabolism ; Substance P ; pharmacology

<p>BACKGROUNDThe possible role of substance P (SP) during wound healing has been the primary research focus in recent years, but its effect on the healing process after bile duct injury is little understood. This study aimed to investigate the effects of SP on growth of fibroblast-like cells derived from rabbit bile duct.p><p>METHODSFibroblast-like cells derived from rabbit bile duct were identified and divided randomly into control and experimental groups. SP-treated cells at different concentrations of 10(-9)-10(-5) mol/L and control group were incubated, respectively, for 48 hours. After incubating, the effects of SP on cell proliferation were assessed by cell counts and MTT test. Apoptosis rate (AR) of cells was measured by flow cytometry.p><p>RESULTSCultured rabbit bile duct cells were fibroblast-like in morphology, and these cells were stained positively for vimentin and negatively for desmin. After SP was added to nonconfluent cells for 48 hours, cell numbers were significantly increased in experimental groups than in controls (P < 0.05). The maximum stimulation of cell proliferation was achieved at SP of 10(-5) mol/L. Bile duct fibroblast-like cells in the SP group showed a higher proliferating activity and lower AR than those in the control group or in the SP + Spantide group (P < 0.05). Spantide partly inhibited the effects of SP on fibroblast-like cells. Examination under transmission electron microscopy revealed rough endoplasmic reticulum and prominent Golgi complexes after SP treatment.p><p>CONCLUSIONSSP has a growth regulatory property on cultivated bile duct fibroblast-like cells in vitro, suggesting that SP may involve in wound healing after bile duct injury by promoting wound fibroblast proliferation and inhibiting apoptosis and participate in pathological scar formation.p>
Animals ; Bile Ducts ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Fibroblasts ; cytology ; drug effects ; Male ; Rabbits ; Substance P ; pharmacology

Animals ; Cells, Cultured ; Cyclic AMP ; metabolism ; Pituitary Gland, Anterior ; cytology ; drug effects ; metabolism ; Rats ; Substance P ; pharmacology

<p>OBJECTIVETo observe the inhibitory effect of mizolastine on substance P(SP)-induced production of leukotriene B(4) (LTB(4)) and interleukin 5 (IL-5) in mouse skin.p><p>METHODSMice were fed with different doses of mizolastine or other control drugs, 30 min after administration animals were injected intradermally with SP on the back. The treated skin samples were taken and competitive enzyme-link immunoassay (ELISA) method was applied to detect LTB (4) and IL-5 in the skin samples.p><p>RESULTThe LTB(4) and IL-5 levels in 10 mg/kg mizolastine group were (1.23 +/-0.29)pg/ml and (34.28 +/-11.00)pg/ml, respectively, which were lower than those in saline control group [(5.52+/-1.88)pg/ml and (179.62 +/-46.25)pg/ml respectively] or loratadine group [(3.89+/-1.27)pg/ml and (127.74 +/-43.27)pg/ml respectively]. No significant difference was found between 10 mg/kg mizolastine group and dexamethasone group (P=0.161 and P=0.508).p><p>CONCLUSIONMizolastine might inhibit the production of LTB(4) and IL-5 induced by substance P in mouse skin, suggesting that anti-inflammatory effect and the blockade of histamine H1 receptors might be involved in its anti-pruritic mechanisms.p>
Animals ; Benzimidazoles ; pharmacology ; Female ; Histamine H1 Antagonists ; pharmacology ; Interleukin-5 ; biosynthesis ; Leukotriene B4 ; biosynthesis ; Male ; Mice ; Mice, Inbred BALB C ; Skin ; metabolism ; Substance P ; antagonists & inhibitors

Spontaneous pain, allodynia and hyperalgesia are well known phenomena following peripheral nerve or tissue injury, and it is speculated that secondary hyperalgesia and allodynia, are generally thought to depend on a hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed that the sensitization may be due to various actions of neurotransmitters (SP, CGRP, excitatory amino acids) released from the primary afferent fibers. In this study, we examined effects of the iontophoretically applied SP and CGRP on the response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn neurones and see if the effects of SP or CGRP mimic the characteristic response pattern known in various pain models. The main results are summarized as follows: 1) SP specifically potentiated NMDA response. 2) CGRP non-specifically potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however, was significantly greater than that of AMPA response. 3) 50% of SP applied cells and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA response and suppression of AMPA response). These results are generally consistent with the sensitization characteristics in diverse pain models and suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA) response are, at least in part, contribute to the development of sensitization in various pain models.
Animal ; Calcitonin Gene-Related Peptide/pharmacology* ; Calcitonin Gene-Related Peptide/administration & dosage ; Excitatory Amino Acid Agonists/pharmacology* ; Iontophoresis ; Male ; N-Methylaspartate/pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/physiology ; Spinal Cord/drug effects* ; Substance P/pharmacology* ; Substance P/administration & dosage ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology

<p>OBJECTIVETo observe the effect of sensory neuropeptide substance P combined with epidermal stem cells (ESC) on wound healing and nerve regeneration in diabetic rats.p><p>METHODSESC that had been isolated from SD rats were identified and cultured in vitro, and they were inoculated onto nourishing layer of amniotic membrane to construct amniotic membrane-ESC. Four full-thickness skin wounds were produced on the back of each of 48 diabetic rats. The resulted 192 wounds were randomly divided into ESC + substance P group, ESC group, substance P group, and control group according to the lottery method, with 48 wounds in each group. Wounds in ESC + substance P group and ESC group were transplanted with amniotic membrane-ESC, and those in substance P group and control group were transplanted with amniotic membrane. After transplantation, 250 µL substance P in the concentration of 1 × 10(-7) mol/L was injected around and into the middle of the wounds in ESC + substance P group and substance P group, 2 times a day, and continued for 4 days, while 250 µL PBS solution was injected in the above-mentioned position in ESC group and control group as control, 2 times a day, and continued for 4 days. On post injury day (PID) 4, 7, 10, 14, 17, and 23, the wound healing rate (with 8 wounds at each time point) was observed and determined, and changes in wound tissue structure were observed with HE staining. On PID 4, 7, and 10, collagen distribution in wound tissue was observed with Masson staining, and type I and type III collagen deposition in wound tissue was respectively observed after immunohistochemical staining. The distribution of protein gene product 9.5 (PGP 9.5) and regeneration of substance P positive nerve fibers in wound tissue were observed with immunohistochemical staining on PID 14 and 23. Data were processed with one-way analysis of variance and t test.p><p>RESULTS(1) The wound healing rate in ESC + substance P group reached 100.0% on PID 14, which was obviously earlier than that in ESC group, substance P group, and control group, healing was respectively observed on PID 17, 17, and 23. The wound healing quality in ESC + substance P group was better than that in the other three groups as shown by HE staining. (2) On PID 10, collagen that was darkly stained and widely distributed was observed in wound tissue of ESC + substance P group and substance P group, while collagen in the other two groups was lightly stained and narrowly distributed. Deposition quantity of type I collagen gradually increased, and that of type III collagen gradually decreased in the wounds of each group over time. On PID 4, 7, and 10, distribution amount of type I collagen in wound tissue of ESC + substance P group was significantly higher than that in ESC group (with t value respectively 32.72, 118.21, 26.71, P values all below 0.01) and control group (with t value respectively 44.37, 22.76, 30.32, P values all below 0.01), while there was no significance between ESC + substance P group and substance P group. On PID 4, 7, and 10, distribution amount of type III collagen in wound tissue of ESC + substance P group was significantly higher than that in ESC group (with t value respectively 32.27, 28.68, 14.51, P values all below 0.01) and control group (with t value respectively 35.68, 22.52, 22.24, P values all below 0.01). (3) A large amount of PGP 9.5 and regeneration of substance P positive nerve fibers, and some peripheral nerve fibers in deep wound extending to epidermis were observed in wound tissue of ESC + substance P group and substance P group. A small amount of PGP 9.5 and regeneration of substance P positive nerve fibers without peripheral nerve fibers extending to epidermis were observed in deep wound tissue of ESC group and control group. On PID 14, 23, ratios of area of PGP 9.5 positive nerve fiber in the wounds of ESC + substance P group were (3.86 ± 0.25)% and (7.03 ± 0.28)%, and they were significantly higher than those of ESC group [(1.48 ± 0.30)%, (3.01 ± 0.43)%, with t value respectively 23.95, 30.27, P values all below 0.01] and control group [(1.46 ± 0.23)%, (2.84 ± 0.29)%, with t value respectively 27.35, 40.32, P values all below 0.01]. On PID 14, 23, ratios of substance P positive nerve fiber area in the wounds of ESC + substance P group were (2.01 ± 0.14)% and (1.19 ± 0.11)%, which were obviously higher than those of ESC group [(0.85 ± 0.17)%, (1.34 ± 0.21)%, with t value respectively 20.50, 2.60, P < 0.05 or P < 0.01] and control group [(0.74 ± 0.15)%, (1.30 ± 0.17)%, with t value respectively 23.98, 2.41, P < 0.05 or P < 0.01].p><p>CONCLUSIONSJoint application of substance P and ESC can effectively promote healing of wound and nerve regeneration in diabetic rats.p>
Animals ; Diabetes Mellitus, Experimental ; pathology ; Epithelial Cells ; cytology ; Nerve Regeneration ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; cytology ; Substance P ; pharmacology ; therapeutic use ; Wound Healing

<p>OBJECTIVETo study the changes in plasma substance P (SP) and calcitonin gene-related peptide (CGRP) levels in children with acute asthma before and after gamma-aminobutyric acid (GABA) treatment.p><p>METHODSSeventy-five children with asthma were randomly assigned to GABA treatment (n=36) and control groups (n=39). Both groups were given conventional treatment for asthma. Besides the conventional treatment, the treatment group was administered with oral GABA (25-30 mg/kg•d). Plasma content of SP and CGRP was measured using ELISA before treatment and after remission.p><p>RESULTSThere were no significant differences in plasma content of SP and CGRP between the GABA treatment and control groups (P＞0.05) before treatment. Plasma content of SP and CGRP in the GABA treatment group was significantly lower than the control group (SP: 57±15 pg/mL vs 127±12 pg/mL; CGRP: 23±10 pg/mL vs 42±8 pg/mL) after remission (P<0.01). Plasma content of SP and CGRP after remission was significantly lower than before treatment (P<0.01) in both groups. There was a significantly positive correlation between plasma SP and CGRP content in asthmatic children (r=0.792, P<0.01).p><p>CONCLUSIONSGABA can significantly decrease plasma levels of SP and CGRP in children suffering from acute asthma.p>
Asthma ; blood ; drug therapy ; Calcitonin Gene-Related Peptide ; blood ; Child ; Child, Preschool ; Female ; Humans ; Male ; Substance P ; blood ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

<p>OBJECTIVETo explore the relationship between neuropeptide substance P (SP) and wound healing in scalded rats.p><p>METHODS(1) Scalded rats with different degrees of scald injury were employed as the experimental model and were sacrificed at 24 post scald hour (PSH), and on 3, 7 and 14 post scald days (PSD). The SP content in the wound was detected with radioimmunoassay method. (2) The murine granulation tissue fibroblasts (GTF) were cultured with different culture media, and divided into control, SP and Spantide (SP receptor antagonism) groups. The effects of SP and Spantide on the cellular activity and apoptotic rate of murine GTF were assessed in vitro.p><p>RESULTSThere was significant difference of the SP content among the superficial (145 +/- 78) ng/g, partial (94 +/- 48 ng/g) and full thickness (53 +/- 27 ng/g) scald wounds at 24 PSH (P < 0.01), while the SP content in partial thickness burn wound on 3 and 7 PSD obviously increased; and that in deep partial thickness burn wound obviously increased on 7 and 14 PSD. But the SP content remained unchanged in full thickness scald wound. (2) SP could promote the activity of GTF and inhibit its apoptosis (The GTF activity in control, SP groups were 0.21 +/- 0.05, 0.36 +/- 0.07, respectively, P < 0.01). Spantide could inhibit the interaction between SP and GTF.p><p>CONCLUSIONSP can promote GTF proliferation, and the SP content in wound is closely associated with the depth of the injury and wound healing capacity.p>
Animals ; Burns ; metabolism ; pathology ; Cell Proliferation ; Disease Models, Animal ; Female ; Fibroblasts ; cytology ; Male ; Rats ; Rats, Wistar ; Receptors, Neurokinin-1 ; metabolism ; Substance P ; analogs & derivatives ; pharmacology ; Wound Healing

<p>OBJECTIVETo investigate the effect of sensory neuropeptide substance P (SP) on the differentiation of cultured epidermal stem cells (ESC) in vitro,with in vitro cultured ESC as the platform.p><p>METHODSESC from newborn Wistar rats were isolated, purified by repeated passages in culture. SP was added for stimulation when ESC clone grew. Immunohistochemistry staining with K14 antibody, and flow cytometry (FCM) was performed at 0, 24th, 48th, 72nd, 96th, 144th, 192nd, 240th, 288th, 336th, 384th, 432nd post differentiation hours (PDH) to identify the cell groups and to detect if there were transient amplifying cells (TAC) among the cells.p><p>RESULTSESC in culture formed large colonies after SP treatment with positive staining for K14, indicating that they were TACs. The results of FCM indicated that when ESC were stimulated by SP, TAC colony formation occurred and the cell number increased in a constant speed.p><p>CONCLUSIONESC could differentiate into TAC by neuropeptide SP induction, and the number of ESC kept on a certain level during the process.p>
Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Endothelial Cells ; cytology ; Female ; Flow Cytometry ; Male ; Rats ; Rats, Wistar ; Sensory Receptor Cells ; chemistry ; Stem Cells ; cytology ; Substance P ; pharmacology