Selective effects of acute and chronic ethanol exposure on neuropeptide and guanine nucleotide stimulated phospholipase C activity in intact N1E-115 neuroblastoma.
The influence of acute and chronic ethanol exposures on the coupling of neurotensin and bradykinin receptors to phospholipase C was determined in intact N1E-115 cells. Phospholipase C was monitored by the formation of total [3H]inositol phosphates in the presence of lithium in cells prelabeled with [3H]inositol. Acute exposure to ethanol over a range of 50 to 200 mM inhibited the stimulation of [3H]inositol phosphate formation elicited by neurotensin and bradykinin. In cells chronically exposed to 100 mM ethanol for 7 days, neither basal- nor neurotensin-stimulated [3H]inositol phosphate formation differed significantly from those of control (untreated) cells. In contrast, the [3H]inositol response to bradykinin was significantly inhibited in cells chronically exposed to ethanol. Because chronic ethanol exposure had no parallel effects on either the specific binding of [3H]bradykinin or the stimulation of [3H]inositol phosphate formation by the stable GTP analog, guanine 5'-(y-thiotriphosphate), it is suggested that chronic ethanol impairs the ability of bradykinin receptors to activate the guanine nucleotide binding protein associated with phospholipase C. In addition, because chronic ethanol had no effect on the inositol phosphate response to neurotensin, it is proposed that certain types of receptor-guanine nucleotide binding protein interactions are more vulnerable than are others to disruption by chronic ethanol treatment.
Smith
T L
TL
Research Service, Department of Veterans Affairs Medical Center, Tucson, Arizona.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology; D009496:Neurotensin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010738:Type C Phospholipases / Q000032:analysis*
D007295:Inositol Phosphates; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009496:Neurotensin; D000431:Ethanol; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D001920:Bradykinin