Lithium homeostasis in Xenopus oocytes: implications for the study of signal transduction.
The Xenopus oocyte has been shown to be a useful model for the study of signal transduction pathways. The present study investigated whether or not the oocyte could be used to study the effects of lithium on signal transduction mechanisms by comparing the dynamics of lithium homeostasis in the oocyte and a human immortalized hippocampal cell line using Flame Atomic Emission Spectroscopy (FAES). A biphasic pattern of lithium uptake was observed in the oocyte in the presence of 5 mM extracellular lithium. The late phase of lithium uptake, which started after 30 minutes of incubation time, was sensitive to phloretin, an inhibitor of Na+/Li+ counter-transport. Differences in lithium efflux kinetics further characterized the two observed phases of accumulation and also suggested that lithium might be distributed in different pools within the oocyte, including one sequestered in organelles or associated with cytosolic proteins. An analogous sequestered pool was not, however, observed in the hippocampal cell line indicating that lithium is distributed differently in these cell types. This suggests that the Xenopus oocyte might not be a suitable model for evaluating the effects of lithium on signal transduction pathways because of the unknown contribution of the sequestered pool on predicting relevant physiological effects.
Gomez
J R
JR
Department of Pharmacology, University of Florida Medical College, J. H. Miller Health Center, Gainesville 32610-0267, USA.
Karkanias
N B
NB
Lenox
R H
RH
Papke
R L
RL
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D008094:Lithium / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D010042:Ouabain; D008094:Lithium; D010693:Phloretin