COMPARATIVE-STUDIES OF PHOSPHOINOSITIDE HYDROLYSIS INDUCED BY ENDOTHELIN-RELATED PEPTIDES IN CULTURED CEREBELLAR ASTROCYTES, C6-GLIOMA AND CEREBELLAR GRANULE CELLS

Effects of endothelin (ET) homologues (ET-1,2,3 and sarafotoxin S6b) and its precursor (big ET-1) on phosphoinositide (PI) turnover were compared in neurally-related cell cultures. All ET-related peptides induced a robust increase of PI turnover in cerebellar astrocytes, C6-glioma and cerebellar granule cells. The rank order of potency in stimulating PI turnover was ET-1=ET-2>-S6b>ET-3>big ET-1 for granule cell neurons, while it was ET-1>-ET-2>-S6b>big ET-1>ET-3 for astrocytes and C6-glioma cells. Short-term pretreatment with phorbol dibutyrate (PDBu) attenuated the ET-1-induced PI response in all three types of cultures. However, long-term pretreatment with PDBu attenuated the response in granule cells and C6-gliomas, but enhanced responses to ET and ATP in astrocytes. Long-term exposure of cells to pertussis toxin (PTX) attenuated the PI response to ET in astrocytes and C6-gliomas, but not in granule cells. Thus, phospholipase C-coupled ET receptors are expressed in both neurons and glial cells, but they differ considerably in their pharmacological selectivity and signal transduction mechanisms in stimulating PI hydrolysis. © 1990.