Hormonal regulation of concentrative nucleoside transport in liver parenchymal cells.
Na(+)-dependent uridine uptake is stimulated in isolated rat liver parenchymal cells by glucagon. This effect is transient, reaches maximum levels of stimulation 10 min after hormone addition, and is dose-dependent. Glucagon action can be mimicked by agents that are able to hyperpolarize the plasma membrane (e.g. monensin) and by dibutyryl cyclic AMP. The effects triggered by glucagon, monensin and dibutyryl cyclic AMP are not additive, suggesting a common mechanism of action. 8-(4-Chloro-phenylthio)adenosine 3':5'-cyclic monophosphate (PCT), a cyclic AMP analogue but also a nucleoside analogue, markedly stimulates Na(+)-dependent uridine uptake in an additive manner to that triggered by monensin, similarly to the effect described for nitrobenzylthioinosine. Considering the roles reported for nucleosides in liver metabolism, the use of PCT as a cyclic AMP analogue should be precluded. Insulin is also about to up-regulate Na(+)-dependent uridine uptake by a mechanism which involves a stable induction of this transport activity at the plasma-membrane level. This is consistent with a mechanism involving synthesis and insertion of more carriers into the plasma membrane. It is concluded that the recently characterized hepatic concentrative nucleoside transporter is under short-term hormonal regulation by glucagon, through mechanisms which involve membrane hyperpolarization, and under long-term control by insulin. This is the first report showing hormonal modulation of the hepatic concentrative nucleoside transporter.
Gomez-Angelats
M
M
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain.
del Santo
B
B
Mercader
J
J
Ferrer-Martinez
A
A
Felipe
A
A
Casado
J
J
Pastor-Anglada
M
M
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D033703:Nucleoside Transport Proteins; D009705:Nucleosides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D014529:Uridine / Q000378:metabolism
D002352:Carrier Proteins; D007328:Insulin; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D009705:Nucleosides; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003994:Bucladesine; D005934:Glucagon; D008985:Monensin; D012964:Sodium; D000242:Cyclic AMP; D014529:Uridine