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 V₁ 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 V₁ antagonist (Pmp¹-O-Me-Tyr²-[Arg⁸]vasopressin, 1 μM) abolished vasopressin Ca²⁺ response in both cell types. Inhibitors of intracellular Ca²⁺ mobilization, thapsigargin (5 μM) and U-73122 (3 μM), 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 V₁-like receptor and involves the mobilization of intracellular Ca²⁺ through an IP₃-or thapsigargin-sensitive Ca²⁺ pool.