Hepatocanalicular organic-anion transport is regulated by protein kinase C.
In order to investigate the regulation of canalicular organic-anion transport, we used a hepatocyte transport assay in which canalicular secretion of a model organic anion, dinitrophenyl-glutathione (GS-DNP), was measured in the presence of stimulators and inhibitors of the Ca2+/protein kinase C (PKC) second-messenger system and of the cyclic AMP (cAMP) second-messenger system. Vasopressin (24 nM) and the phorbol ester phorbol 12-myristate 13-acetate (1 microgram/ml), both stimulators of PKC, stimulated GS-DNP efflux by 65 +/- 36% and 55 +/- 28% respectively, whereas staurosporine (10 microM), an inhibitor of PKC, inhibited efflux by 53 +/- 13%. Glucagon and forskolin, both stimulators of the cAMP second-messenger system, as well as the cAMP analogue dibutyryl cAMP and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, did not significantly influence the GS-DNP efflux. It can be concluded that canalicular organic-anion transport in hepatocytes is either directly or indirectly regulated by PKC.
Roelofsen
H
H
Division of Gastrointestinal and Liver Diseases, Academic Medical Centre, Amsterdam, The Netherlands.
Ottenhoff
R
R
Oude Elferink
R P
RP
Jansen
P L
PL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins; D000838:Anions; D001648:Bile Canaliculi / Q000378:metabolism*; D001692:Biological Transport; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D000470:Alkaloids; D027321:Anion Transport Proteins; D000838:Anions; D002352:Carrier Proteins; D014667:Vasopressins; D005576:Colforsin; C030190:S-(2,4-dinitrophenyl)glutathione; D003994:Bucladesine; D005934:Glucagon; D000242:Cyclic AMP; D011493:Protein Kinase C; D005978:Glutathione; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine