Cholera toxin resistance associated with deficient adenylate-cyclase activity in a subclone of the rat promyelocytic leukemia (BNML).
The rat promyelocytic leukemia cell line BNML is highly sensitive to cAMP elevating agents, and to cholera toxin (CT) in particular: 99.9% of the cells are killed in less than 48 hr of toxin treatment. We described here a subclone of the same leukemia, which, in contrast, is completely resistant to CT but still sensitive to other cAMP inducers. This locates the defect responsible for CT resistance at the membrane, somewhere between surface CT receptors and adenylate cyclase. CT-resistant BNML cells (CTR-BNML) do have surface CT receptors (several thousands per cell). Adenylate cyclase activity in CTR-BNML cells is not stimulated by cholera toxin. Other GS mediated stimulation of adenylate cyclase (by PGE, isoproterenol, histamine, NaF) remains relatively high, though 25-60% lower than in CTS-BNML cells. These results suggest that a specific adenylate cyclase defect is involved in the resistance of CTR-BNML cells to cholera toxin.
Hermouet
S
S
Laboratoire d'Oncologie et Immunohématologie, Hôpital Saint-Louis, Paris, France.
Lanotte
M
M
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D004351:Drug Resistance; D005677:G(M1) Ganglioside; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology*; D051381:Rats; D011914:Rats, Inbred BN; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C023552:choleragen receptor; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases