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)

The effects of substance P (SP) and its new structural analog EC-1 administered systemically to CBA mice on the immune responsiveness have been examined. Three main findings are presented in this study. First, the principal effect of SP and EC-1 on the immunity is a stimulatory one. It is shown that in the doses of 1, 10 and 100 mkg/kg of the body weight both neuropeptides significantly increased the number of plaque- and rosette-forming cells in the spleen of animals at the peak of the immune reactions. Second, the destruction of the pituitary stalk prevented the immune response stimulation caused by neuropeptides. Third, SP-induced immunostimulation was not observed after combination with the antagonist of the postsynaptic dopamine (DA) D-2 receptors haloperidol (2 mg/kg) suggesting the involvement of the DAergic system in the realization of this effect. Thus, these results demonstrate neurochemical DAergic mechanisms underlying the immunostimulating influence of tachykinins.
 ...
PMID:Neuropeptides in the immunomodulation: substance P-induced stimulation of immune response in mice. 963 49

Several viruses are known to utilize cellular integrin molecules to gain entry into cells. Because of the ability of herpes simplex virus type 1 (HSV-1) to disrupt cellular adhesion, as seen particularly in ocular infections, we examined the ability of several peptides, containing known integrin recognition sequences, to interfere with plaque formation of HSV-1 in epithelial cells. We also examined the possible involvement of tachykinins in virus entry. We did not detect any decrease in plaque formation by HSV-1 in the presence of Arg-Gly-Asp, Asp-Gly-Glu-Ala, or EILDV peptides or in the presence of monoclonal antibodies to the human beta1 or beta4 integrin subunit. Substance P or inhibitors of the NK1 or NK2 tachykinin receptors also had no inhibitory effects on HSV-1 plaque formation.
 ...
PMID:Lack of detectable interaction between HSV-1 and integrins or tachykinins. 982 Aug 48

Our previous ex vivo and in vivo studies reported that expression of the recombinant endothelial nitric oxide (NO) synthase (eNOS) gene in adventitial fibroblasts recovers NO production in arteries without endothelium in response to bradykinin. The present study was designed to characterize subtypes of bradykinin receptors on adventitial fibroblasts coupled to the activation of recombinant eNOS. Endothelium-denuded segments of canine basilar arteries were transduced with beta-galactosidase (beta-Gal) gene or eNOS gene ex vivo, using a replication-defective adenoviral vector (10(10) plaque-forming units/ml) for 30 min at 37 degrees C. Twenty-four hours later, isometric force recording or cGMP measurement was carried out. B(1) bradykinin receptor agonist (des-Arg(9)-bradykinin, 10(-10)-10(-8) mol/l) did not significantly affect vascular tone in control or beta-Gal gene-transduced canine basilar arteries without endothelium. In contrast, this agonist caused concentration-dependent relaxations in recombinant eNOS gene-transduced arteries without endothelium. Relaxations to B(1) receptor agonist in the eNOS arteries were abolished by B(1) receptor antagonist (des-Arg(9)-[Leu(8)]bradykinin, 6 x 10(-9) mol/l) but not by B(2) receptor antagonist (Hoe-140, 5 x 10(-8) mol/l). Bradykinin did not significantly alter vascular tone in control or beta-gal arteries without endothelium, whereas this peptide (10(-11)-10(-8) mol/l) induced concentration-dependent relaxations, as well as an increase in cGMP formation in endothelium-denuded eNOS-transduced arteries. Stimulatory effects of bradykinin were prevented in the presence of a B(2) receptor antagonist but not in the presence of a B(1) receptor antagonist. B(1) and B(2) receptor antagonists had no effect on relaxations to substance P, confirming the selectivity of the compounds. Our results suggest that B(1) and B(2) bradykinin receptors are coupled to activation of recombinant eNOS expressed in adventitial fibroblasts.
 ...
PMID:B(1) and B(2) bradykinin receptors on adventitial fibroblasts of cerebral arteries are coupled to recombinant eNOS. 1066 66

Resistance arteries are an important target for vascular gene therapy because they play a key role in the regulation of tissue blood flow. The present study was designed to determine the effects of recombinant endothelial (e) nitric oxide synthase (NOS) gene expression on vasomotor reactivity of small brain stem arteries (internal diameter, 253 +/- 2.5 microm). Arterial rings were exposed ex vivo to an adenoviral vector (10(9) and 10(10) plaque-forming units/ml) encoding eNOS gene or beta-galactosidase gene. Twenty-four hours after transduction, vascular function was examined by isometric force studies. Transgene expression was evident mainly in adventitia. In arteries with endothelium transduced with eNOS gene but not with control beta-galactosidase gene, relaxations to bradykinin and substance P were significantly augmented. Removal of endothelium abolished relaxations to bradykinin and substance P in control and beta-galactosidase arteries. However, in endothelium-denuded arteries transduced with recombinant eNOS, bradykinin and substance P caused relaxations that were abolished in the presence of the NOS inhibitor N(G)-nitro-L-arginine methyl ester. In control arteries, endothelium removal augmented relaxations to the nitric oxide donors sodium nitroprusside and diethylamine NONOate. This augmentation was absent in eNOS gene-transduced arteries without endothelium. Our results suggest that, in small brain stem arteries, expression of recombinant eNOS increases biosynthesis of nitric oxide. Adventitia of small arteries is a good target for expression of recombinant eNOS. Genetically engineered adventitial cells may serve as a substitute source of nitric oxide in cerebral arteries with dysfunctional endothelium.
 ...
PMID:Effects of recombinant eNOS gene expression on reactivity of small cerebral arteries. 1066 71

Immunohistochemistry was used to analyse 18- and 26-month-old transgenic mice overexpressing the human beta-amyloid precursor protein under the platelet-derived growth factor-beta promoter with regard to presence and distribution of neuropeptides. In addition, antisera/antibodies to tyrosine hydroxylase, acetylcholinesterase, amyloid peptide, glial fibrillary acidic protein and microglial marker OX42 were used. These mice have been reported to exhibit extensive amyloid plaques in the hippocampus and cortex [Masliah et al. (1996) J. Neurosci. 16, 5795-5811]. The most pronounced changes were related to neuropeptides, whereas differences between wild-type and transgenic mice were less prominent with regard to tyrosine hydroxylase and acetylcholinesterase. The main findings were of two types; (i) involvement of peptide-containing neurites in amyloid beta-peptide positive plaques, and (ii) more generalized changes in peptide levels in specific layers, neuron populations and/or subregions in the hippocampal formation and ventral cortices. In contrast, the parietal and auditory cortices were comparatively less affected. The peptide immunoreactivities most strongly involved, both in plaques and in the generalized changes, were galanin, neuropeptide Y, cholecystokinin and enkephalin. This study shows that there is considerable variation both with regard to plaque load and peptide expression even among homozygotes of the same age. The most pronounced changes, predominantly increased peptide levels, were observed in two 26-month-old homozygous mice, for example, galanin-, enkephalin- and cholecystokinin-like immunoreactivities in stratum lacunosum moleculare, and galanin, neuropeptide Y, enkephalin and dynorphin in mossy fibers. Many peptides also showed elevated levels in the ventral cortices. However, decreases were also observed. Thus, galanin-like immunoreactivity could not any longer be detected in the diffusely distributed (presumably noradrenergic) fiber network in all hippocampal and cortical layers, and dynorphin-like immunoreactivity was decreased in stratum moleculare, cholecystokinin-like immunoreactivity in mossy fibers and substance P-like immunoreactivity in fibers around granule cells. The significance of generalized peptide changes is at present unclear. For example, the increase in the mainly inhibitory peptides galanin, neuropeptide Y, enkephalin and dynorphin and the decrease in the mainly excitatory peptide cholecystokinin in mossy fibers (and of substance P fibers around granule cells) indicate a shift in balance towards inhibition of the input to the CA3 pyramidal cell layer. Moreover, it may be speculated that the increase in levels of some of the peptides represents a reaction to nerve injury with the aim to counteract, in different ways, the consequences of injury, for example by exerting trophic actions. Further studies will be needed to establish to what extent these changes are typical for Alzheimer mouse models in general or are associated with the V717F mutation and/or the platelet-derived growth factor-beta promoter.
 ...
PMID:Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein--initial observations. 1100 66

APPsw transgenic mice showing substantial features of brain Abeta amyloidosis such as senile plaques and behavioral abnormalities were examined by immunostaining to determine whether Abeta deposits could induce the subsequent disturbance of neurotransmitter systems including somatostatin, substance P and choline acetyltransferase (ChAT), which are prominent in the Alzheimer's disease brain. Somatostatin, substance P and ChAT disappeared in the areas of senile plaque and were accumulated in dystrophic neurites around the amyloid cores. These findings suggest a potential role of brain Abeta amyloidosis in disturbance of the neurotransmitter systems leading to memory disturbance of Alzheimer's disease.
 ...
PMID:Impaired neurotransmitter systems by Abeta amyloidosis in APPsw transgenic mice overexpressing amyloid beta protein precursor. 1101

The effects of a GH secretagogue, L-692,585 (L-585), and human GH-releasing hormone (hGHRH) on calcium transient and GH release were investigated in isolated porcine pituitary cells using calcium imaging and the reverse hemolytic plaque assay (RHPA). Somatotropes were functionally identified by the application of hGHRH. All cells that responded to hGHRH responded to L-585 application. Perfusion application of 10 microM hGHRH and L-585 for 2 min resulted in an increase in intracellular calcium concentrations ([Ca(2+)](i)) of 53+/-1 nM (mean+/-S.E.M.) (P < 0.01) and 68+/-2 nM (P < 0.01) respectively. The L-585 response was characterized by an initial increase in [Ca(2+)](i) followed by a decline to a plateau level above the baseline. Concurrent calcium imaging with RHPA indicated that the L-585-evoked increase in [Ca(2+)](i) coincided with GH release. L-585 significantly increased the percentage of plaque-forming cells (24+/-3 vs 40+/-6%; P < 0.05) and mean area of plaques (1892+/-177 vs 3641+/-189 micro m(2); P < 0.01) indicating increased GH release. Substance P (SP) analogue ([d -Arg(1),d -Phe(5),d -Trp(7,11)]-SP) blocked, and the hGHRH receptor antagonist ((Phenylac-Tyr(1),d -Arg(2), p-chloro-Phe(6), Homoarg(9), Tyr (Me)(10), Abu(15), Nle(27),d -Arg(28), Homoarg(29))-GRF (1-29) amide) decreased the stimulatory effect of hGHRH. These failed to block the stimulatory effect of L-585, suggesting a different receptor for L-585 from the GHRH receptor. The hGHRH-induced calcium transients and initial peak increase induced by L-585 were significantly decreased by removal of calcium from the bathing medium or the addition of nifedipine, an L-calcium channel blocker. The plateau component of L-585-induced calcium change was abolished by removal of calcium and nifedipine. These results suggest an involvement of calcium channels in GH release. Either SQ-22536, an adenylate cyclase inhibitor, or U73122, a phospholipase C (PLC) inhibitor, blocked the stimulatory effects of hGHRH and L-585 on [Ca(2+)](i) transient, indicating the involvement of adenylate cyclase-cAMP and PLC-inositol triphosphate pathways. These results further suggested that calcium mobilization from internal stores during the first phase of the L-585 response induced an increase in [Ca(2+)](i) whereas calcium influx during the second phase is a consequence of somatotrope depolarization.
 ...
PMID:Mechanism of action of the growth hormone secretagogue, L-692,585, on isolated porcine somatotropes. 1247 74

Neurogenic inflammation is markedly potentiated in airways that are infected with respiratory syncytial virus (RSV). Aims of this study were to determine whether this potentiation persists after the virus is cleared, investigate the mechanism of postviral potentiation, and define whether prophylaxis with a MAb against the RSV fusion protein (palivizumab) prevents this effect. Thirty days after inoculation, no evidence of active RSV infection was found in the airway epithelium by plaque assay or immunostaining and no viral nucleic sequences were detected by PCR, yet capsaicin-induced plasma extravasation in the airways that were infected 30 d earlier with RSV was still significantly larger compared with pathogen-free controls. Substance P content in lung tissues and capsaicin-induced release of this peptide from sensory nerves were significantly increased at 30 d. The administration of palivizumab 24 h before virus inoculation prevented the development of abnormal neurogenic inflammatory responses. Our data suggest that the airways remain abnormally susceptible to the proinflammatory effects of sensory nerves after RSV infection is cleared, as a result of changes in sensory innervation, and that this abnormality can be prevented by passive prophylaxis against RSV.
 ...
PMID:Persistent airway inflammation after resolution of respiratory syncytial virus infection in rats. 1471 92

Metabolism by peptidases plays an important role in modulating the levels of biologically-active neuropeptides, while that of substance P (SP), a component of gingival crevicular fluid (GCF), may potentiate the inflammatory process in orthodontic tooth movement. The aim of this study was two-fold: (1) to investigate GCF levels of SP and interleukin-1beta (IL-1beta) during human orthodontic tooth movement, and (2) to determine the correlation coefficients between SP and IL-1beta levels in the GCF. The subjects were 3 males, with a mean age of 21.3 +/- 2.8 years old, and 6 females, with a mean age of 23.1 +/- 2.4 years, undergoing orthodontic movement of a single tooth, with the contralateral tooth used as the control. GCF was sampled at the control and treatment (compression) sites before and 1, 4, 8, 24, 72, 120, and 168 hours after initiation of orthodontic treatment. Prevention of plaque-induced inflammation allowed assessment of the dynamics of mechanically stimulated SP and IL-1beta levels in the GCF, which were determined using enzyme-linked immunosorbent assay (ELISA) kits. GCF levels of SP and IL-1beta for the treated teeth were significantly higher (P < 0.001) than for the corresponding control teeth from 8 to 72 hours, and peaked at 24 hours. These results show that the amounts of SP and IL-1beta in GCF increase with orthodontic tooth movement, and indicate that such increases may be involved in inflammation in response to mechanical stress.
 ...
PMID:Relationship between substance P and interleukin-1beta in gingival crevicular fluid during orthodontic tooth movement in adults. 1637 50

To probe the mechanisms by which respiratory syncytial virus (RSV) infection in early life forms an important risk factor for the development of chronic asthma, an airway hyper-responsiveness (AHR) animal model of guinea-pigs with persistent RSV infection was established by intranasal instillation of 2 x 10(5) plaque-forming units RSV. On days 0, 7, 28, 42 and 60 postinoculation, the RSV copy numbers, airway function and peptidergic innervation were measured in the peripheral airways. The results showed that the virus was persistent in the lungs. During persistent infection (days 42 and 60), the lung resistance and the total cells, neutrophils and eosinophils of infected guinea-pigs increased significantly; the airway showed signs of chronic inflammation; and the substance P- and calcitonin gene-related peptide-positive fibres increased, but vasoactive intestinal polypeptide-positive fibres decreased. These results suggest that persistent RSV infection can cause long-term chronic airway inflammation and persistent airway neural network abnormality, which may be related to the occurrence of AHR.
 ...
PMID:Infection with respiratory syncytial virus alters peptidergic innervation in the lower airways of guinea-pigs. 1860


<< Previous 1 2 3 4 Next >>