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)

Treatment of Sprague-Dawley rats with the compound LS 2616, a quinoline-3-carboxamide, enhanced the delayed-type hypersensitivity response (DTH) to recall antigens as judged by the specific accumulation of inflammatory cells after challenge with Bordetella pertussis in the pleural space. LS 2616 was effective when given both before sensitization and at the time of secondary antigen challenge. The effect of LS 2616 on DTH was dose-dependent. LS 2616 was highly effective in enhancing DTH in rats with suppressed cell-mediated immunity after treatment with anti-thymocyte globulin or prednisolone, indicating its possible value in the immunosuppressed state.
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PMID:Effects of the novel immunomodulator LS 2616 on the delayed-type hypersensitivity reaction to Bordetella pertussis in the rat. 287 88

The role of protein kinase C alpha 2-adrenoceptor-induced contractions of rabbit saphenous vein was investigated. Contractions induced by the alpha 2-adrenoceptor-selective agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoline (UK14304) were inhibited by prior treatment with pertussis toxin and by Ca2+ removal, confirming a Gi/Go-dependent coupling pathway which was highly dependent upon Ca2+ influx. Protein kinase C inhibitors calphostin-C and staurosporine each caused a non-competitive inhibition of UK14304 response. Down-regulation of protein kinase C by pretreatment with tetradecanoylphorbol acetate reduced UK14304 response by almost 90% with no effect on contractions induced by elevated KCl. The ineffectiveness of L-type Ca2+ channel blockers and the absence of stimulated 45Ca2+ uptake or efflux by UK14304 indicated that phospholipid-derived products were most likely responsible for protein kinase C activation. alpha 2-Adrenoceptor stimulation failed to increase [3H]myoinositol phosphate formation, but caused a significant increase in the formation of both [32P]phosphatidic acid and diacylglycerol, indicating the possible activation of phospholipase D activity. These results suggest that protein kinase C is important for the vasoconstriction induced by alpha 2-adrenoceptors and that diacylglycerol derived from receptor-initiated phospholipase D activity may provide protein kinase C stimulation.
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PMID:Involvement of protein kinase C activation in alpha 2-adrenoceptor-mediated contractions of rabbit saphenous vein. 763 71

Linomide (LS-2616, quinoline-3-carboxamide) is a synthetic immunomodulator that stimulates natural killer cell activity and activates several lymphocytic subpopulations in experimental animals and humans. In this study we determined the effect of oral treatment with linomide on the development of experimental autoimmune encephalomyelitis, an animal model for immune-mediated human demyelinating disorders. Experimental autoimmune encephalomyelitis was induced in SJL/J mice and in an outbred strain of rats (Sabra) by subcutaneous injection of spinal cord homogenate in adjuvant followed by inoculation with Bordetella pertussis. Linomide was administered in drinking water, at an estimated dose of 50 to 100 mg/kg/day. None of the linomide-treated mice (0/41) and Sabra rats (0/15) developed any clinical or pathological signs of experimental autoimmune encephalomyelitis, whereas almost all control animals (48/53 and 18/19, respectively) were severely paralyzed and 64.5% died from the disease. Lymphocytes obtained from linomide-treated animals had reduced in vitro proliferative responses to guinea pig myelin basic protein, proteolipid protein of the myelin, and tuberculin-purified protein derivative, unlike antigen-independent proliferation which was rather unaffected. Natural killer cell activity (tested by a cytotoxic assay on radiolabeled YAC-1 target cells) was significantly enhanced in mice treated with linomide. Our results indicate that modulation of the immune system with linomide leads to complete inhibition of experimental autoimmune encephalomyelitis in the absence of systemic immunosuppression. Linomide could therefore be of use in future clinical trials for the treatment of human autoimmune demyelinating disorders.
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PMID:Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide. 823 57