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)

Every year in the United States, respiratory syncytial virus (RSV) infections in infants and young children cause more than 120,000 hospitalizations, often complicated by the need for mechanical ventilation; yet no effective therapy is currently available for this disease. We showed previously that RSV infection is associated with neurogenic inflammation in the lower respiratory tract. In the present study, we sought to determine whether aerosolized beta(2)-receptor agonists inhibit neurogenic-mediated albumin extravasation in the airways of RSV-infected, mechanically ventilated rats, and to compare the anti-inflammatory effects of racemic albuterol ((RS)-albuterol) to its individual enantiomeric components (R)-albuterol and (S)-albuterol. Albumin extravasation evoked by sensorineural stimulation with capsaicin was inhibited only partially by 0.63 mg (RS)-albuterol, and higher doses had minimal incremental effects. In contrast, the anti-inflammatory effect of (R)-albuterol was already larger at the lowest dose of 0.31 mg, and complete inhibition of neurogenic exudation was observed at higher doses. (S)-albuterol had no significant inhibitory effect up to 1.25 mg, and had only partial inhibitory effect at higher doses. The anti-inflammatory effect of (R)-albuterol was independent from the expression of substance P neurokinin 1 receptors, suggesting a direct vascular effect. Our data show that (R)-albuterol has a much stronger inhibitory effect on neurogenic inflammation in RSV-infected airways when aerosolized in enantiomerically pure form, rather than in a racemic mixture with (S)-albuterol. Based on these data, we speculate that (R)-albuterol may be more effective than other adrenergic agents in the management of bronchiolitis.
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PMID:Anti-inflammatory effect of albuterol enantiomers during respiratory syncytial virus infection in rats. 1595 75

The neuropeptide substance P (SP) has been implicated in the disruption of the blood-brain barrier (BBB) and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg), dexamethasone (8 mg/kg) or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05). Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants further investigation as a potential anti-edematous treatment.
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PMID:Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors. 2481 61