Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the in vitro airway and tissue responses to antigen and the involvement of the potential mediators serotonin (5-HT) and leukotriene D4 (LTD4). We sensitized Brown-Norway rats with ovalbumin (OA) and subsequently challenged bronchial rings and subpleural parenchymal strips with OA in the organ bath. In selected experiments tissues were incubated with methysergide (a 5-HT receptor antagonist), ketanserin (a 5-HT2 receptor antagonist), MK-571 (a LTD4 receptor antagonist), or MK-886 (5-lipoxygenase inhibitor) prior to challenge. Both bronchial rings and parenchymal strips constricted in response to OA. Methysergide and ketanserin completely inhibited OA-induced constriction of bronchial rings. The effect of MK-571 was not significant, whereas MK-886 partially blocked OA-induced bronchial constriction, suggesting a potential role for LTC4 in antigen-induced airway constriction. In parenchymal strips, methysergide, ketanserin, MK-571, and MK-886 all partially inhibited the OA response, whereas the combinations of methysergide and MK-571 or ketanserin and MK-886 completely ablated the response. These data suggest that both bronchial rings and parenchymal strips constrict after OA challenge but that the relative contributions of 5-HT and LTD4 to the allergic response in central airways and parenchymal tissues differ.
 ...
PMID:In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4. 759 67

The Brown Norway rat produces high levels of IgE in response to active immunization and develops both early and late airway constrictor responses after subsequent allergen challenge. We have used this model of allergic asthma to investigate the temporal relationship between the in vivo synthesis of peptidoleukotrienes (peptido-LTs) and the late response. Brown Norway rats that had been sensitized by injection of ovalbumin 2 to 3 wk prior to the commencement of the experiment were subjected to bile duct cannulation and tracheal intubation. The rats were challenged 2 h later by intratracheal instillation of ovalbumin. Lung resistance was measured before and at frequent intervals after antigen challenge. Biliary peptido-LTs (LTC4, LTD4, LTE4, and N-acetyl-LTE4) were measured by a combination of high pressure liquid chromatography and radioimmunoassay in bile samples collected for a period of 1 h before instillation of ovalbumin, and between zero and 1 h, 1 and 4 h, 4 and 6 h, and 6 and 8 h, subsequently. All of the 10 rats subjected to antigen challenge developed early responses. Of these, six also developed late responses, whereas two died about 1 h after challenge. The levels of peptido-LTs excreted in bile between 4 and 8 h after antigen challenge (corresponding in time to the late responses) were about four times higher in the ovalbumin-instilled rats that developed late responses (n = 6) than in the ovalbumin-sensitized control rats that had been subjected to instillation of saline (n = 6; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Leukotrienes in bile during the early and the late airway responses after allergen challenge of sensitized rats. 842 Apr 2

Smokers are less likely to develop some inflammatory and allergic diseases. In Brown-Norway rats, nicotine inhibits several parameters of allergic asthma, including the production of Th2 cytokines and the cysteinyl leukotriene LTC(4). Cysteinyl leukotrienes are primarily produced by mast cells, and these cells play a central role in allergic asthma. Mast cells express a high-affinity receptor for IgE (FcepsilonRI). Following its cross-linking, cells degranulate and release preformed inflammatory mediators (early phase) and synthesize and secrete cytokines/chemokines and leukotrienes (late phase). The mechanism by which nicotine modulates mast cell activation is unclear. Using alpha-bungarotoxin binding and quantitative PCR and PCR product sequencing, we showed that the rat mast/basophil cell line RBL-2H3 expresses nicotinic acetylcholine receptors (nAChRs) alpha7, alpha9, and alpha10; exposure to exceedingly low concentrations of nicotine (nanomolar), but not the biologically inactive metabolite cotinine, for > or = 8 h suppressed the late phase (leukotriene/cytokine production) but not degranulation (histamine and hexosaminidase release). These effects were unrelated to those of nicotine on intracellular free calcium concentration but were causally associated with the inhibition of cytosolic phospholipase A(2) activity and the PI3K/ERK/NF-kappaB pathway, including phosphorylation of Akt and ERK and nuclear translocation of NF-kappaB. The suppressive effect of nicotine on the late-phase response was blocked by the alpha7/alpha9-nAChR antagonists methyllycaconitine and alpha-bungarotoxin, as well as by small interfering RNA knockdown of alpha7-, alpha9-, or alpha10-nAChRs, suggesting a functional interaction between alpha7-, alpha9-, and alpha10-nAChRs that might explain the response of RBL cells to nanomolar concentrations of nicotine. This "hybrid" receptor might serve as a target for novel antiallergic/antiasthmatic therapies.
 ...
PMID:Nicotine inhibits Fc epsilon RI-induced cysteinyl leukotrienes and cytokine production without affecting mast cell degranulation through alpha 7/alpha 9/alpha 10-nicotinic receptors. 2050 47