Effects of histamine on polyphosphoinositide metabolism in NG108-15 cells

Effects of histamine on metabolism of phosphatidylinositol and its related phospholipids were studied in NG108-15 cells. Histamine (100 ?M) significantly caused formation of both inositol trisphosphate (IP(3)) and inositol bisphosphate (IP(2)) in NG108-15 cells whose phosphatidylinositol was prelabelled with [(3)H]inositol. Histamine at 1-100 ?M dose-dependently caused the degradation of phosphatidylinositol 4,5-bisphosphate (PI-4,5-P(2)) and phosphatidic acid (PA) in the cells prelabelled with [(3)H]arachidonic acid. Histamine degraded PI-4,5-P(2) in a biphasic manner which reached two peaks at 10 and 30 s. The degradation at 30 s was inhibited by pretreatment with 100 ?M quinacrine, while it was not affected at 10 s. In addition, 100 ?M quinacrine significantly abolished histamine-induced degradation of PA at 10 and 30 s. Although 100 ng/ml pertussis toxin pretreatment for 4 h resulted in ADP-ribosylation of 41 kDa membrane proteins, histamine-induced PI-4,5-P(2) degradation was not significantly affected by the toxin treatment. These results suggest that: (1) histamine causes polyphosphoinositide degradation by phospholipase C and further by phospholipase A(2); (2) histamine presumably stimulates PA-specific phospholipase A(2), resulting in the decrease of PA and release of arachidonic acid and/or the metabolites; (3) 41 kDa GTP-binding proteins ADP-ribosylated by pertussis toxin were not involved in histamine receptor-mediated polyphosphoinositide turnover in NG108-15.