Mechanical stimulation of airway epithelial cells generates the Ca²⁺ mobilization messenger inositol 1,4,5-trisphosphate and the protein kinase (PK) C activator diacylglycerol. Inositol 1,4,5-trisphosphate diffuses through gap junctions to mediate intercellular communication of the mechanical stimulus (a "Ca²⁺ wave"); the role that diacylglycerol-activated PKC might play in the response is unknown. Using primary cultures of rabbit tracheal cells, we show that 12-O-tetradecanoylphorbol 13-acetate- or 1,2-dioctanyl-sn-glycerol-induced activation of PKC slows the Ca²⁺ wave, decreases the amplitude of induced intracellular free Ca²⁺ concentration ([Ca²⁺]_i) increases, and decreases the number of affected cells. The PKC inhibitors bisindolylmaleimide and Gö 6976 slowed the spread of the wave but did not change the number of affected cells. We show that ATP-induced [Ca²⁺]_i increases and oscillations, responses independent of intercellular communication, were inhibited by PKC activators. Bisindolylmaleimide decreased the amplitude of ATP-induced [Ca²⁺]_i increases and blocked oscillations, suggesting that PKC has an initial positive effect on Ca²⁺ mobilization and then mediates feedback inhibition. PKC activators also reduced the [Ca²⁺]_i increase that followed thapsigargin treatment, indicating a PKC effect associated with the Ca²⁺ release mechanism.

protein kinase C; adenosine 5'-triphosphate; mechanotransduction; purinergic receptor; phospholipase C

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