P2Y-purinoceptor regulation of surfactant secretion from rat isolated alveolar type II cells is associated with mobilization of intracellular calcium.
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 greater than adenosine 5'-O-(3-thiotriphosphate) (gamma S-ATP) greater than beta, gamma-imido adenosine 5'-triphosphate (AMPPNP) greater than beta, gamma-methylene adenosine 5'-triphosphate (beta, gamma-CH2-ATP) greater than alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-CH2-ATP). The respective EC50S were 10(-6) M, 2 X 10(-6) M, 2 X 10(-5) M, and greater than 2.5 X 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 = gamma S-ATP greater than AMPPNP greater than alpha, beta-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) beta, gamma-CH2-ATP was a more potent secretagogue than alpha, beta-CH2-ATP and (c) the rank orders of agonist potency for calcium mobilization and phospholipid secretion were the same.
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University of Cincinnati, College of Medicine, Department of Pediatrics, Ohio 45267-0541.
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D002118:Calcium