Mechanism of S100b release from rat cortical slices determined under basal and stimulated conditions.
Incubation of rat cortical slices in a medium that was not containing oxygen and glucose (oxygen-glucose deprivation, OGD) caused a 200% increase in the release of S100B. However, when slices were transferred to a medium containing oxygen and glucose (reoxygenation conditions, or REO), S100B release reached 500% of its control value. Neither inhibition of nitric oxide (NO) synthase by L-NAME nor addition of the NO donors sodium nitroprussid (SNP) or hydroxylamine (HA) to the medium altered basal S100B release. Similarly, the presence of SNP, HA or NO precursor L: -arginine in the medium, or inhibition of NO synthase by L-NAME also failed to alter OGD- and REO-induced S100B outputs. Moreover, individual inhibition of PKC, PLA(2) or PLC all failed to attenuate the S100B release determined under control condition or enhanced by either OGD or REO. Blockade of calcium channels with verapamil, chelating the Ca(+2) ions with BAPTA or blockade of sodium channels with tetrodotoxin (TTX) did not alter OGD- and REO-induced S100B release. In contrast to the pharmacologic manipulations mentioned above, glutamate and alpha-ketoglutarate added at high concentrations to the medium prevented both OGD- and REO-induced S100B outputs. These results indicate that neither NO nor the activation of PKC, PLA(2) or PLC seem to be involved in basal or OGD- and REO-induced S100B outputs. Additionally, calcium and sodium currents that are sensitive to verapamil and TTX, respectively, are unlikely to contribute to the enhanced S100B release observed under these conditions.
Gürsoy
Murat
M
Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Uludağ University, 16059, Bursa, Turkey.
Büyükuysal
R Levent
RL
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism; D066298:In Vitro Techniques; D007656:Ketoglutaric Acids / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007656:Ketoglutaric Acids; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D007770:L-Lactate Dehydrogenase; D052248:Nitric Oxide Synthase Type I; D005947:Glucose; D010100:Oxygen