Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the mechanism of contraction induced by S1P in esophageal smooth muscle cells. Western blot analysis demonstrated that S1P(1), S1P(2), S1P(3), and S1P(5) receptors existed in the cat esophagus. Only penetration of EDG-5 (S1P(2)) antibody into permeabilized cells inhibited S1P-induced contraction. Pertussis toxin (PTX) also inhibited contraction, suggesting that it was mediated by S1P(2) receptors coupled to a PTX-sensitive G(i) protein. Specific antibodies to G(i2), G(q) and G(beta) inhibited contraction, implying that the S1P-induced contraction depends on PTX-insensitive G(q) and G(beta) dimers as well as the PTX-sensitive G(i2). Contraction was not affected by the phospholipase A2 inhibitor DEDA, or the PLD inhibitor rho-chloromer-curibenzoate, but it was abolished by the PLC inhibitor U73122. Incubation of permeabilized cells with PLCb3 antibody also inhibited contraction. Contraction involved the activation of a PKC pathway since it was affected by GF109203X and chelerythrine. Since PKCepsilon antibody inhibited contraction, PKCe may be required. Preincubation of the muscle cells with the MEK inhibitor PD98059 blocked S1P-induced contraction, but the p38 MAP kinase inhibitor SB202190 did not. In addition, co-treatment of cells with GF 109203X and PD98059 did not have a synergistic effect, suggesting that these two kinases are involved in the same signaling pathway. Our data suggest that S1P-induced contraction in esophageal smooth muscle cells is mediated by S1P(2) receptors coupled to PTX-sensitive G(i2) proteins, and PTX-insensitive G(q) and G(beta) proteins, and that the resulting activation of the PLCb3 and PKCepsilon pathway leads to activation of a p44/p42 MAPK pathway.
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PMID:Sphingosine 1-phosphate-induced signal transduction in cat esophagus smooth muscle cells. 1651 46

Pertussis toxin (PTX) is an ancillary adjuvant used to elicit experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. One mechanism whereby PTX potentiates EAE is to increase blood-brain barrier (BBB) permeability. To elucidate further the mechanism of action of PTX on the BBB, we investigated the genomic and proteomic responses of isolated mouse brain endothelial cells (MBEC) following intoxication. Among approximately 14,000 mouse genes tracked by cDNA microarray, 34 showed altered expression in response to PTX. More than one-third of these genes have roles in angiogenesis. Accordingly, we show that intoxication of MBEC induces tube formation in vitro and angiogenesis in vivo. The global effect of PTX on signaling protein levels and phosphorylation in MBEC was investigated by using Kinex antibody microarrays. In total, 113 of 372 pan-specific and 58 of 258 phospho-site-specific antibodies revealed changes >or=25% following intoxication. Increased STAT1 Tyr-701 and Ser-727 phosphorylation; reduced phosphorylation of the activating phospho-sites in Erk1, Erk2, and MAPKAPK2; and decreased phosphorylation of arrestin beta1 Ser-412 and Hsp27 Ser-82 were confirmed by Kinetworks multi-immunoblotting. The importance of signal transduction pathways on PTX-induced MBEC tube formation was evaluated pharmacologically. Inhibition of phospholipase C, MEK1, and p38 MAP kinase had little effect, whereas inhibition of cAMP-dependent protein kinase, protein kinase C, and phosphatidylinositol 3-kinase partially blocked tube formation. Taken together, these findings are consistent with the concept that PTX may lead to increased BBB permeability by altering endothelial plasticity and angiogenesis.
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PMID:Pertussis toxin induces angiogenesis in brain microvascular endothelial cells. 1850 Jul 52


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