Regulation of lung surfactant secretion by the A sub 2 adenosine receptor

The authors previously reported that adenosine (A) stimulates secretion of phosphatidylcholine (PC), the major component of surfactant, in type II pneumocytes. To determine how this effect is mediated we examined the effect of P{sub 1} purinoceptor agonists -N{sup 6}-phenylisoprpyl-A (PIA), 5{prime}-N-ethylcarboxyamido-A (NECA), 2-chloro-A (CA) - and antagonists - theophylline (T) and 8-phenyltheophylline (8PT) - on PC secretion and cAMP levels in type II cells isolated from the adult rat. The cells were preincubated with {sup 3}H-choline for 20 h, transferred to fresh medium and incubated {plus minus} test agents for 1.5 h after which {sup 3}H-PC in the cells and medium was measured. A and its analogs stimulated PC secretion in a dose-dependent manner. At the optimal concentration (A, 1 mM; analogs, 0.01 mM) secretion was stimulated approx. 2-fold from a basal rate of 0.08-1.02% of total PC in the medium after 1.5 h. The potency order was NECA>CA=L-PIA>A>D-PIA. The EC{sub 50} for NECA was 8.9 {times} 10{sup {minus}8}M. The effect of NECA was significantly inhibited by 8PT (0.01 mM) and T (0.05 mM). NECA, A and L-PIA increased cellular cAMP levels 34, 12 and 8 fold, respectively, from a basal level of 0.23-0.28 pmol/10{sup 6} cells. These data suggestmore » that the A{sub 2} subtype of the P{sub 1} receptor mediates the effect of A. In newborn rabbits, lung lavage PC increased form 24.1 {plus minus} 1.6 ug P/g lung dry wt at 0 h to 62.6 {plus minus} 7.7 after breathing for 3 h (n=13). 8PT (15 mg/kg, i.m.) at 0 h decreased the PC content at 3 h by 29% to 44.4 {plus minus} 5.1 ug/g. This suggests a functional role for the P{sub 1} receptor in lung surfactant secretion.« less