Uncoupling of intracellular cyclic AMP and dome formation in cultured canine kidney epithelial cells: effects of gangliosides and vasopressin.
Cultured MDCK cells were treated with various gangliosides and sialylated compounds and their effects on the intracellular level of cAMP were compared to those of arginine vasopressin (AVP) and other substances which elevate cAMP. Since all those agents could stimulate dome formation, its correlation with cAMP production is discussed. Most gangliosides increased intracellular cAMP 3-4-fold, the increase being dose-dependent up to 25 microM ganglioside. AVP and cAMP analogs increased intracellular cAMP 3-40-fold. A unique feature of the ganglioside-induced cAMP increase was its extremely long time course (70 h), as compared to that induced by other agents which show much faster and less prolonged effects in other biological systems. This might indicate that gangliosides differ from AVP and other agents in the mechanisms by which they stimulate intracellular cAMP increase. The time course and the level of cAMP increase induced by GM3 or AVP did not correlate with those of dome formation. Furthermore, the ability of some gangliosides and other agents to induce dome formation did not correspond to their ability to elevate cAMP. It is suggested that although the remarkable dome-stimulating activity of gangliosides may be induced in part by a cAMP-dependent mechanism, gangliosides also act directly on the cellular components influencing dome formation, without involving changes in intracellular cAMP.
Rodrig
N
N
Department of Biochemistry, Faculty of Medicine, University of Tokyo.
Osanai
T
T
Iwamori
M
M
Nagai
Y
Y
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D005679:G(M3) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D009439:Neuraminidase / Q000378:metabolism; D011402:Pronase / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D005679:G(M3) Ganglioside; D005732:Gangliosides; D014475:Uncoupling Agents; D014667:Vasopressins; D000242:Cyclic AMP; D009439:Neuraminidase; D011402:Pronase