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

WR Rice, FM Singleton - British journal of pharmacology, 1987 - Wiley Online Library
WR Rice, FM Singleton
British journal of pharmacology, 1987Wiley Online Library
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 …
  • 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.
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