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)

The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion and on smooth muscle tone. Because mast cells release proteases during degranulation, and are located in many of the same tissue microenvironments into which SP and VIP are released, we wished to examine whether mast cell proteases, by cleaving and thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations of the two major neutral proteases of mast cell granules, tryptase and chymase, to determine the sites and rates of cleavage of SP and VIP. The proteases were purified from dog mastocytomas. Tryptase cleaved VIP rapidly at two sites with a kcat/Km of 2.2 X 10(5) sec-1 M-1, but had no effect on SP. Chymase cleaved both SP and VIP at primarily a single site with kcat/Km of 3.9 X 10(4) and 5.4 X 10(4) sec-1 M-1, respectively. Thus, these data show that mast cell proteases degrade SP and VIP. The differences in peptidase activity between tryptase and chymase suggest that the consequences of protease release could vary according to mast cell protease phenotype and location in various tissues and species. Tryptase, by cleaving the bronchodilator VIP but not the bronchoconstrictor SP, might promote bronchial hyper-responsiveness in asthma by decreasing the nonadrenergic neural inhibitory influence mediated by VIP. In skin and other tissues, chymase might interrupt axon reflex-mediated neurogenic inflammation by cleaving SP.
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PMID:Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. 244 73

Chymase shows a catalytic efficiency in the formation of angiotensin (Ang) II. In the present study, the characterization and primary structure of monkey chymase were determined, and the pathophysiological role of chymase was investigated on the atherosclerotic monkey aorta. Monkey chymase was purified from cheek pouch vascular tissue using heparin affinity and gel filtration columns. The enzyme rapidly converted Ang I to Ang II (Km = 98 microM, k(cat) = 6203/min) but did not degrade several peptide hormones such as Ang II, substance P, vasoactive intestinal peptide and bradykinin. The primary structure, which was deduced from monkey chymase cDNA, showed a high homology to that of human chymase (98%). The mRNA levels of the aorta chymase were significantly increased in the atherosclerotic aorta of monkeys fed a high-cholesterol diet. These results indicate that monkey chymase has a highly specific Ang II-forming activity and may be related to the pathogenesis of atherosclerosis.
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PMID:Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta. 925 95

Human cord blood-derived mast cells (HCMC) grown in medium with serum and recombinant human stem cell factor (rhSCF) with or without interleukin (IL)-6 are less mature than human skin mast cells (HSMC). We found that c-kit-positive HCMC cultured for 8-10 weeks with rhSCF in serum-free medium became sensitive to basic secretatogues and expressed the serine protease, chymase, which is preferentially expressed in HSMC. The HCMC release beta-hexosaminidase (beta-HEX) within 1 min of stimulation with compound 48/80 or substance P, and release was suppressed by pertussis toxin. Approximately 34% of the HCMC in the serum-free culture stained positively with chymase antibody. Chymase and c-kit levels, and responsiveness to basic secretagogues, increased substantially after an additional 2 weeks in a serum-free environment with rhIL-6 and rhSCF. Moreover, Fc(epsilon)RI-dependent activation of the HCMC resulted in induction of cytokines and cyclooxygenase-2. These results show that HCMC can differentiate into a phenotype morphologically and functionally similar to HSMC if exposed to SCF in serum-free medium.
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PMID:Degranulation and cytokine expression in human cord blood-derived mast cells cultured in serum-free medium with recombinant human stem cell factor. 1465 Dec 55

Human mast cells are categorized into mast cells positive only for tryptase (MC(T)) and mast cells positive for both tryptase and chymase (MC(TC)). The structural appearance of tryptase-, and chymase-positive mast cells in metastatic liver disease and the variations in MC(T) and MC(TC) numbers in accordance with the origin of the primary tumors have been described in the present study. Liver mast cells are analyzed immunocytochemically using tryptase and chymase and by quantitative morphometry in 30 patients with colorectal (n = 15), gastric (n = 8), and pancreatic (n = 7) cancers and in 5 control livers. The numbers of MC(T) and MC(TC) are increased in the extratumoral liver tissue (mainly portal tracts) as compared to controls. The numbers of MC(T) and MC(TC) in and around metastases with moderate or high grade of differentiation are statistically significantly higher, as compared to those with low grades of differentiation. The numbers of MC(TC) are greater than that of MC(T) in the extratumoral liver tissue and in metastases themselves. Ultrastructurally, mast cells immunostained with tryptase and chymase have three types of granules: electron dense granules with darkly precipitated reaction product, electron lucent granules without reaction product and electron lucent granules with sparse reaction product (altered granules). Both types of mast cells have small and large in size granules, resembling the MC(TC) phenotype described earlier. Tryptase-positive mast cells have granules with discrete scrolls and particulate and beaded pattern. Chymase-positive mast cells have granules with finely granular or particulate material. Substance P (SP)- and vasointestinal polypeptide (VIP)-positive mast cells are not observed in livers with metastases. The present study suggests that liver mast cells are mainly from the MC(TC) type, and are accumulated in peritumoral and metastatic areas. They may play a role in the formation of tumor stroma, or in tumor immunology in liver metastases from various primary gastrointestinal cancers.
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PMID:Structural examination of tryptase- and chymase-positive mast cells in livers, containing metastases from gastrointestinal cancers. 1466 92