Interleukin-1 beta stimulation of 45Ca2+ release from rat striatal slices.
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.
Plami
M
M
Istituto di Scienze Farmacologiche, University of Siena, Italy.
Frosini
M
M
Sgaragli
G
G
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002614:Chelating Agents; D007375:Interleukin-1; D010726:Phosphodiesterase Inhibitors; D010566:Virulence Factors, Bordetella; D002110:Caffeine; D004533:Egtazic Acid; D037342:Pertussis Toxin; D009543:Nifedipine; D002118:Calcium