Endothelin-1 stimulates the release of preloaded [3H]D-aspartate from cultured cerebellar granule cells.
We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded [3H]D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca2+, but was unaffected by 1 mM Co2+ or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system.
Lin
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WW
NIMH Neuroscience Center, St. Elizabeths, Washington, D.C. 20032.
Lee
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CY
Chuang
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DM
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D016232:Endothelins; D004730:Endothelium, Vascular; D007536:Isomerism; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016232:Endothelins; D010455:Peptides; D010566:Virulence Factors, Bordetella; D014316:Tritium; D001224:Aspartic Acid; D015240:Phorbol 12,13-Dibutyrate; D003035:Cobalt; D011189:Potassium Chloride; D037342:Pertussis Toxin; D002118:Calcium