Heterologous desensitization of bradykinin-induced phosphatidylinositol response and Ca2+ mobilization by neurotensin in NG108-15 cells.
The heterologous desensitization of the bradykinin (BK)-induced increase in intracellular Ca2+ concentration ([Ca2+]i) by neurotensin was studied in neuroblastoma x glioma hybrid NG108-15 cells. The addition of neurotensin to the cells resulted in an increase in [Ca2+]i and an increase in the formation of inositol phosphates in Ca2+-free medium. Pretreatment of the cells with neurotensin resulted in 43% decrease in the BK-induced increase of [Ca2+]i. The increase in [Ca2+]i induced by ionomycin, which causes Ca2+ release from the intracellular pool, was not decreased by pretreatment with neurotensin. This indicates that the inhibitory effect of neurotensin on the BK-induced increase of [Ca2+]i was not due to depletion of the intracellular Ca2+ pool. Pretreatment with neurotensin also caused a 47% decrease in the BK-induced formation of inositol trisphosphates (IP3). This decrease was not due to depletion of phosphatidylinositol bisphosphates. Neurotensin did not inhibit [3H]BK binding to cell membranes. These results show that neurotensin desensitizes the BK responses of NG108-15 cells, heterologously, perhaps by changes in phospholipase C and/or guanine nucleotide-binding protein (G-protein).
Imaizumi
T
T
Department of Pharmacology I, Osaka University School of Medicine, Japan.
Osugi
T
T
Misaki
N
N
Uchida
S
S
Yoshida
H
H
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016257:Fura-2; D005910:Glioma / Q000378:metabolism*; D007295:Inositol Phosphates / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D009496:Neurotensin / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D001572:Benzofurans; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D009496:Neurotensin; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2