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

A brief exposure of pancreatic islets to the cytokine interleukin-1 beta (IL-1 beta) induces an initial stimulatory phase, which is followed by inhibition of islet function and eventually beta-cell damage. In the present study we have investigated the effects of IRAP, a blocker of type I IL-1 receptor and actinomycin D, an inhibitor of DNA transcription, on both the stimulatory and inhibitory effects of IL-1 beta on rat pancreatic islets in vitro. The two test agents counteracted the initial stimulatory actions of IL-1 beta on both islet glucose-induced insulin release and glucose oxidation rates. Furthermore, cycloheximide, an inhibitor of protein synthesis, could also prevent the early IL-1 beta-induced stimulation of insulin release. When islets were exposed for 1 hr to IL-1 beta and studied after 12 hr, there was a 75% inhibition of glucose induced insulin release, a 50% decrease in glucose oxidation rates and a 30% decrease in (pro)insulin biosynthesis. These effects were completely counteracted by coincubation with IRAP or actinomycin D, but were not affected by coincubation with pertussis toxin. Islet exposure to IL-1 alpha also induced a 60-80% inhibition of glucose-induced insulin release after 12 hr. As observed with rIL-1 beta, IRAP was also able to block the suppressive effects of IL-1 alpha on islet function. Mouse islets exposed for 2 hr to IL-1 beta and studied after 12 hr presented a 50% decrease in the glucose-induced insulin release. This effect was completely blocked by coincubation with a rat monoclonal antibody generated against the type I mouse IL-1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of receptor binding and gene transcription for both the stimulatory and inhibitory effects of interleukin-1 in pancreatic beta-cells. 153 17

1. Previous observations that centrally injected interleukin-1 beta (IL-1 beta) into rabbits induces a sustained rise in cerebrospinal fluid (CSF) Ca2+ concentration ([Ca2+]) as well as fever, prompted us to undertake an in vitro study to corroborate the in vivo results and gain insight as to the source and mechanism of IL-1 beta-induced Ca2+ mobilization. 2.IL-1 beta treatment of rat striatal slices preloaded with 45Ca2+ elicited a rise in spontaneous 45Ca2+ release which was dose-dependent, delayed in onset and of extended duration. At concentrations of 1, 5 and 10 ng ml-1, the 45Ca2+ efflux increased by 6.3 +/- 1.3 (s.e. mean), 33.4 +/- 5.0 and 159 +/- 10.5% respectively. 3. At 1 microgram ml-1, the specific IL-1 receptor antagonist, IRAP, antagonised the effect induced by, 10 ng ml-1 IL-1. 4. Caffeine 10 mM,which failed to release calcium on its won, potentiated IL-1-elicited 45Ca2+ release. 5. Perfusion with a Ca(2+)-free medium obtained by use of excess EGTA (3 mM) or in the presence of the Ca2+ channel blocker, nifedipine (3 x 10(-8 M) abolished the potentiating effect of caffeine without affecting the IL-1-induced 45Ca2+ release. 6. Preincubation of slices for 4 h with Bordetella pertussis toxin (PTX, 1.3 micrograms ml-1) did not change the pattern of Ca2+ efflux in response to IL-1. 7. In conclusion, these data indicate that IL-1 stimulates calcium release from brain tissue by a specific, receptor-mediated mechanism which partly depends on extracellular calcium but does not involve a PTX-sensitive G protein as part of the transducing signal.
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PMID:Interleukin-1 beta stimulation of 45Ca2+ release from rat striatal slices. 884 35