Introduction of aromatic ring-containing substituents in cyclic nucleotides is associated with inhibition of toxin uptake by the hepatocyte transporters OATP 1B1 and 1B3.

ABSTRACT: Analogs of the cyclic nucleotides cAMP and cGMP have been extensively used to mimic or modulate cellular events mediated by protein kinase A (PKA), Exchange protein directly activated by cAMP (Epac), or protein kinase G (PKG). We report here that some of the most commonly used cyclic nucleotide analogs inhibit transmembrane transport mediated by the liver specific organic anion transporter peptides OATP1B1 and OATP1B3, unrelated to actions on Epac, PKA or PKG. Several cAMP analogs, particularly with 8-pCPT-substitution, inhibited nodularin (Nod) induced primary rat hepatocyte apoptosis. Inhibition was not mediated by PKA or Epac, since increased endogenous cAMP, and some strong PKA- or Epac-activating analogs failed to protect cells against Nod induced apoptosis. The cAMP analogs inhibitin

SUBMITTER: Herfindal L 

PROVIDER: S-EPMC3989234 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature