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)

Protease-activated receptors are G protein-coupled receptors activated by serine-proteases. Protease-activated receptor 2 is involved in the regulation of airway smooth muscle tone but its effects vary according to species and experimental conditions. We determined the effects of protease-activated receptor 2 activation on smooth muscle tone and airway reactivity to histamine in guinea pigs and smoking or non-smoking humans. The effects of trypsin and protease-activated receptor activating peptide on the isometric tension and response to histamine of guinea pig tracheal and human bronchial rings were studied. Human tissues were obtained from 6 smokers and 4 non-smokers. We assessed the effects of epithelial removal, inhibitors of cyclooxygenases, nitric oxide synthases, neutral endopeptidase and antagonists of acetylcholine, histamine, bradykinin and tachykinin receptors. Bronchomotor responses to protease-activated receptor 2 activation were variable in guinea pig, in half of animals PAR2 activation induced smooth muscle relaxation through the epithelial release of prostanoids but not of nitric oxide. In human airways, protease-activated receptor 2 activation reduced responsiveness to histamine in bronchial rings from smokers but increased responsiveness in bronchi from non-smokers. This study demonstrates an influence of tobacco smoking on the effect of protease-activated receptor 2 activation on airway responsiveness in humans, with an increased protection against histamine-induced contractions, probably through an increased epithelial release of prostanoids. The role of airway protease-activated receptor 2 may be to maintain smooth muscle tone homeostasis.
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PMID:Protease-activated receptor 2 in regulation of bronchomotor tone: effect of tobacco smoking. 1519 59

Protease-activated receptor 2 (PAR2) is activated by trypsin and mast cell tryptase to induce widespread inflammation by unknown mechanisms. Trypsin and tryptase were shown to activate sensory neurons to release substance-P and related peptides to mediate neurogenic inflammation. In the present study, the expression of PAR2 and tachykinins were investigated in rat trigeminal neurons that were identified by retrograde labeling with rhodamine dye from the nasal mucosa by using neuronal tracing in combination with immunohistochemistry. We found that large subpopulation of all trigeminal neurons (43.5+/-2.6%) identified by the pan-neuronal marker PGP 9.5 were stained with PAR2-immunoreactivity. Of all trigeminal neurons, 7.5+/-2.1% were immunoreactive for tachykinins and PAR2, and only 3.9+/-1.7% of all trigeminal neurons expressed tachykinins, but not PAR2-immunoreactivity. The present study also found that a large number trigeminal neurons innervating the nasal mucosa expressed PAR2-immunoreactivity. Of the rhodamine-labeled trigeminal neurons, 52.5+/-1.8% were immunoreactive for only PAR2 expression, 7.3+/-1.9% contained tachykinins and PAR2, and 3.1+/-0.4 of the rhodamine-labeled trigeminal neurons were non-immunoreactive PAR2, but were positive for tachykinins-immunoreactivity. In conclusion, based on the co-localization of PAR2 and tachykinins in trigeminal sensory neurons innervating the nasal mucosa, the present study suggests that, following an activation of PAR2 receptor in tachykinergic neurons by trypsin and mast cell tryptase, there may be a triggering of tachykinin-mediated phenomena such as neurogenic inflammation in allergic or non-allergic rhinitis.
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PMID:Protease-activated receptor 2 expression in trigeminal neurons innervating the rat nasal mucosa. 1615 Apr 84