Ionophore A-23187 induced histamine release from rat mast cells and rat basophil leukemia (RBL-1) cells.
Ionophore A-23187 releases histamine from normal mast cells apparently by promoting Ca++ influx (Foreman et al, Nature 245: 249, 1973). In our hands at concentrations of greater than 0.2 mug/ml release occurs in 1 to 2 min, is blocked by metabolic inhibitors, and is unaccompanied by cytotoxicity (trypan-blue uptake, lactic dehydrogenase (LDH) release). At higher doses (0.5 mug/ml) histamine release is followed by significant cytotoxicity, but again Ca++ is required. In parallel studies, we examined cultured rat basophilic leukemia (RBL-1) cells. These cells, which apparently have normal surface receptors for IgE, contained approximately 700 ng histamine/10(6) cells but did not release histamine when IgE-mediated release was looked for. They do not respond to doses of ionophore which would be expected to give non-cytotoxic histamine release. At higher doses histamine release is preceded by progressive LDH release: LDH release is 75% complete at 5 min whereas 10 min are required for 75% maximal histamine release. This reaction requires Ca++ and is temperature dependent but is not inhibited by metabolic poisons (2-deoxyglucose, dinitrophenol, CN-). These studies suggest that either Ca++ does not enter into these cells normally or that one or more mechanisms which are ordinarily triggered by the changes in Ca++ flow are unresponsive in the RBL-1 cells. These studies also underline the importance of ruling out cytotoxicity in ionophore-induced phenomena.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001491:Basophils; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006632:Histamine / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007942:Leukemia, Experimental / Q000276:immunology*; D008274:Magnesium / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology*; D051381:Rats
D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D003486:Cyanides; D000001:Calcimycin; D006632:Histamine; D003847:Deoxyglucose; D004492:Edetic Acid; D007770:L-Lactate Dehydrogenase; D008274:Magnesium; D002118:Calcium