title: Nitric oxide modulation of interleukin-1[beta]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices.
abstract: Intracellular Ca(2+) mobilization and release into mammal CSF plays a fundamental role in the etiogenesis of fever induced by the proinflammatory cytokine interleukin-1beta (IL-1beta) and other pyrogens. The source and mechanism of IL-1beta-induced intracellular Ca(2+) mobilization was investigated using two experimental models. IL-1beta (10 ng/ml) treatment of rat striatal slices preloaded with (45)Ca(2+) elicited a delayed (30 min) and sustained increase (125-150%) in spontaneous (45)Ca(2+) release that was potentiated by l-arginine (300 microm) and counteracted by N-omega-nitro-l-arginine methyl ester (l-NAME) (1 and 3 mm). The nitric oxide (NO) donors diethylamine/NO complex (sodium salt) (0.3 and 1 mm) and spermine/NO (0.1 and 0.3 mm) mimicked the effect of IL-1beta on Ca(2+) release. IL-1beta stimulated tissue cGMP concentration, and dibutyryl cGMP enhanced Ca(2+) release. The guanyl cyclase inhibitors 1H-[1,2, 4]oxadiazole[4,3-a] quinoxalin-1-one (100 microm) and 6-[phenylamino]-5,8 quinolinedione (50 microm) counteracted Ca(2+) release induced by 2.5 but not 10 ng/ml IL-1beta. Ruthenium red (50 microm) and, to a lesser extent, heparin (3 mg/ml) antagonized IL-1beta-induced Ca(2+) release, and both compounds administered together completely abolished this response. Similar results were obtained in human astrocytoma cells in which IL-1beta elicited a delayed (30 min) increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) (402 +/- 71.2% of baseline), which was abolished by 1 mm l-NAME. These data indicate that the NO/cGMP-signaling pathway is part of the intracellular mechanism transducing IL-1beta-evoked Ca(2+) mobilization in glial and striatal cells and that the ryanodine and the inositol-(1,4,5)-trisphosphate-sensitive Ca(2+) stores are involved.
authors: Istituto di Scienze Farmacologiche, Università di Siena, 53100 Siena, Italy.
authors: A
authors: A
authors: Meini
authors: A
authors: A
authors: Benocci
authors: M
authors: M
authors: Frosini
authors: G
authors: G
authors: Sgaragli
authors: G
authors: G
authors: Pessina
authors: C
authors: C
authors: Aldinucci
authors: G T
authors: GT
authors: Youmbi
authors: M
authors: M
authors: Palmi
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D006834:Hydrazines; D007375:Interleukin-1; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D010069:Oxadiazoles; D011810:Quinoxalines; D012430:Ruthenium Red; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D006493:Heparin; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester