Figure 2.

Schematic representation of the mechanisms of regulation of hepatocellular signal transduction by the hepatoprotective agents (TUDC, β-MC, and DBcAMP). TUDC, and presumably β-MC, increase cytosolic Ca²⁺ levels by stimulating both Ca²⁺ release from microsomal inositol-1,4,5-trisphosphate (IP₃) sensitive stores via an IP₃ independent pathway and Ca²⁺ influx from extracellular sources via Ni²⁺ sensitive channels,^17–19 leading to activation of the Ca²⁺ dependent PKC isoform, PKC-α.² DBcAMP, a permeable cAMP analogue, is instrumental in both elevating cytosolic Ca²⁺ and activating PKA. Activation of Ca²⁺, PKC, and PKA dependent pathways may mediate reinsertion of canalicular transporters by stimulating their recycling from the SAC; this may counteract localisation changes of these carriers induced by TLC. To assess the role of these different signal transduction pathways, several inhibitors have been used, including the intracellular Ca²⁺ chelator BAPTA/AM, the PKC inhibitors H7 and SP, and the PKA inhibitor KT5720. BAPTA/AM, 1,2-bis-(o-aminophenoxy)-ethene-N,N,N`,N`-tetra-acetate tetra-(acetomethyl)ester; DBcAMP, dibutyryl-cAMP; β-MC, β-muricholate; PKC-α, protein kinase C α; PKA, protein kinase A; SAC, subapical compartment; SP, staurosporine; TUDC, tauroursodeoxycholate.