Rat oatp1 (Slc21a1) and oatp2 (Slc21a5) transport many structurally unrelated endogenous and exogenous compounds across the sinusoidal membrane of hepatocytes in a sodium-independent manner. There are several potential protein kinase A (PKA) and protein kinase C (PKC) phosphorylation sites in both rat oatp1 and oatp2 proteins, suggesting that PKA and/or PKC may play a role in regulating their function. It is known that the activities of many transporters are subject to the short-term regulation by activation of PKA or PKC, and thus the purpose of the current study was to determine the effect of compounds that activate or inhibit PKA and PKC on the uptake function of rat organic anion transporting protein (oatp)1 and oatp2 when expressed in Xenopus laevis oocytes. In the present investigation, neither the PKA activator N-6-benz-cAMP (0.001-1 mM) nor the PKA inhibitor H7 (0.1-100 μM) affected the uptake mediated by rat oatp1 and oatp2. In contrast, the PKC activator phorbol-12-myristate-13-acetate (PMA) suppressed the uptake mediated by rat oatp1 and oatp2 in a concentration- and time-dependent manner. In addition, pretreatment with bisindolyl-maleimide, a specific PKC inhibitor, partially reversed the suppression of PMA on rat oatp1-, and almost completely reversed the suppression of PMA on rat oatp2-mediated uptake. In conclusion, this study indicates that rat oatp1- and oatp2-mediated uptake is subject to the short-term regulation by PKC activation, but not by PKA activation.
|Original language||American English|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 2001|
ASJC Scopus subject areas
- Molecular Medicine