Mechanism of vasopressin-induced increase in intracellular Ca2+ in LLC-PK1 porcine kidney cells

Analysis of the signal transduction cascade of vasopressin-induced increase in intracellular Ca2+ concentration ([Ca2+](i)) in LLC-PK1 cells was performed. First, a comparison of the effect of vasopressin on [Ca2+](i) in LLC-PK1 cells with that produced in rat hepatocytes was performed [an intracellular mobilizing mechanism involving a V-1 receptor coupled to the production of inositol 1,4,5-trisphosphate (IP3)]. Second, the effect of known inhibitors of intracellular Ca2+ mobilization on vasopressin Ca2+ response in LLC-PK1 cells was studied. Vasopressin induced a transient increase in [Ca2+](i) in both LLC-PK1 cells and hepatocytes. In contrast to the single [Ca2+](i) spike seen in LLC-PK1 cells, vasopressin induced an average of two to three [Ca2+](i) spikes in hepatocytes. The V-1 antagonist (Pmp(1)-O-Me-Tyr(2)-[Arg(8)]vasopressin, 1 mu M) abolished vasopressin Ca2+ response in both cell types. Inhibitors of intracellular Ca2+ mobilization, thapsigargin (5 mu M) and U-73122 (3 mu M), abolished the Ca2+ response by vasopressin in LLC-PK1 cells. The results suggest that vasopressin-induced increase in [Ca2+](i) in LLC-PK1 cells is mediated via a V-1-like receptor and involves the mobilization of intracellular Ca2+ through an IP3- or thapsigargin-sensitive Ca2+ pool.