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Drug
Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P15088 (
mast cell
)
14,925
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Rats were sensitized against egg albumin and the response of the longitudinal muscle from the proximal small intestine to the antigen was tested. Egg albumin (1-100 micrograms/ml) concentration-dependently induced a contraction of the longitudinal muscle in tissues from sensitized animals but not from nonsensitized animals. The response to the antigen was resistant to neuronal blockers like tetrodotoxin, atropine and hexamethonium. Inhibitors of thromboxane synthesis such as the cyclooxygenase inhibitor, indomethacin, the
thromboxane synthase
blocker, 1-benzylimidazole, or the combined cyclooxygenase/lipoxygenase/
thromboxane synthase
inhibitor, sulfasalazine, inhibited the contraction evoked by egg albumin. A similar concentration-dependent inhibition of the antigen response was observed with two thromboxane A2 receptor blockers, SK&F 88046 and KW-3635. None of these blockers affected the response to the muscarinic agonist, carbachol, excluding unspecific effects of the drugs on smooth muscle contractility. The effect of antigen was reduced by the
mast cell
stabilizing agent, quercetin, and by the histamine H1 receptor blocker, mepyramin. These drugs, however, also inhibited the response to carbachol. When contractions were stimulated directly by the stable thromboxane derivative, carbocyclic thromboxane A2, the smooth muscle proved to be more than three orders of magnitude more sensitive to this agonist of the thromboxane pathway compared to histamine. Consequently, thromboxane A2 seems to be one of the main mediators of anaphylactically induced longitudinal muscle contractions in the rat small intestine.
...
PMID:Inhibition of antigen-induced muscle contractions by inhibitors of thromboxane pathway in rat small intestine. 934 27
12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is a 17-carbon hydroxy fatty acid that is biosynthesized either by enzymatic pathways, like
thromboxane synthase
(
TXAS
) and cytochrome P450 or a non-enzymatic pathway.
TXAS
catalyzes the isomerization reaction from PGH
2
to 12-HHT, malondialdehyde, and TXA
2
at a ratio of 1:1:1. Furthermore, 12-HHT has been considered as a mere byproduct of TXA
2
biosynthesis, and its biological function has long been uncertain. BLT2 was initially identified as a low-affinity leukotriene B
4
(LTB
4
) receptor, which is also activated by various hydroxy-eicosatetraenoic acids (HETEs), suggesting that BLT2 may be activated by other endogenous ligands apart from LTB
4
and HETEs. By unbiased ligand screening using crude lipids from rat organs, 12-HHT has been identified as an endogenous agonist for BLT2. The 12-HHT-BLT2 axis induces
mast cell
migration and contributes to allergic inflammation. BLT2 is also expressed in epithelial cells of the small intestine and skin in mice and contributes to in vivo epithelial barrier functions.
...
PMID:Metabolism and biological functions of 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid. 3307 76