P2Y‐purinoceptor regulation of surfactant secretion from rat isolated alveolar type II cells is associated with mobilization of intracellular calcium

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Abstract
1 The effect of methylene, thio, and imido substituted analogues of adenosine 5′-triphosphate (ATP) on surfactant phospholipid secretion and calcium mobilization in rat isolated alveolar Type II cells was studied. 2 ATP was the most potent secretagogue of adenine nucleotides studied. The rank order of agonist potency for [3H]-phosphatidylcholine secretion was ATP > adenosine 5′-O-(3-thiotriphosphate) (γS-ATP) > β, γ-imido adenosine 5′-triphosphate (AMPPNP) > β, γ-methylene adenosine 5′-triphosphate (β, γ-CH2-ATP) > α, β-methylene adenosine 5′-triphosphate (α, β-CH2-ATP). The respective EC50s were 10−6 m, 2 × 10−6 m, 2 × 10−5 m, 5 × 10−5 m, and > 2.5 × 10−4 m. 3 Exogenous ATP also induced a rapid mobilization of intracellular calcium monitored by changes in Fura 2 fluorescence. The rank order of agonist potency for calcium mobilization was similar to the rank order of agonist potency for surfactant secretion: ATP = γS-ATP > AMPPNP > α, β-CH2-ATP. 4 There was no effect of EGTA on ATP-induced calcium mobilization, consistent with the hypothesis that exogenous ATP induces release of calcium from intracellular stores. 5 These data are consistent with a P2Y-purinoceptor regulating surfactant secretion from isolated Type II cells via mobilization of intracellular calcium, since: (a) non-hydrolyzed analogues of ATP are potent secretagogues, (b) β, γ-CH2-ATP was a more potent secretagogue than α, β-CH2-ATP and (c) the rank orders of agonist potency for calcium mobilization and phospholipid secretion were the same.