P2‐purinoceptors regulate surfactant secretion from rat isolated alveolar Type II cells

Abstract

1 Rat isolated alveolar Type II cells were utilized to examine the effect of purine and pyrimidine analogues on secretion of pulmonary surfactant. 2 ATP potently stimulated [³H]-phosphatidylcholine ([³H]-PC) secretion in a time- and dose-dependent manner. The effect of ATP was noted by one hour of exposure and persisted for three hours. The EC₅₀ (concentration producing 1/2 the maximal response) for ATP-induced [³H]-PC secretion was 100 nM. 3 ADP was also a potent secretagogue for surfactant secretion, but AMP and adenosine had no significant effect on surfactant secretion at concentrations < 250 μM. The EC₅₀ for ADP-induced [³H]-PC secretion was 250 nM. 4 Other purine and pyrimidine nucleotides (ITP, GTP, CTP, TTP) were examined for their effect on [³H]-PC secretion. All purine and pyrimidine triphosphates examined significantly augmented [³H]-PC secretion, but were much less potent than ATP. The EC₅₀s were ITP = 10 μM; GTP = 100 μM; CTP = 250 μM; TTP = 100 μM. 5 Neither 8-phenyltheophylline (10 μM, a P₁-purinoceptor antagonist), propranolol (100 μM, a β-adrenoceptor antagonist), nor indomethacin (10 μM, a prostaglandin synthetase inhibitor) inhibited ATP-induced [³H]-PC secretion from isolated Type II cells. 6 These data provide evidence for regulation of surfactant secretion from alveolar Type II cells by a P₂-purinoceptor.