A2 and P2 purine receptor interactions and surfactant secretion in primary cultures of type II cells.
Phosphatidylcholine secretion in type II pneumocytes can be stimulated by P1 (adenosine) and P2 (ATP) purinoceptor agonists. The effect of adenosine is mediated by the A2 subtype of the P1 receptor. The A1 subtype is inhibitory. We examined the influence of ATP and the A2 agonist 5'-(N-ethylcarboxyamido)adenosine (NECA) on phosphatidylcholine secretion in primary cultures of rat type II cells. The stimulatory effects of ATP and NECA were less than additive, suggesting a common mechanism of action. NECA and ATP both caused a rapid increase in cAMP, and the combination enhanced this even further. ATP promoted inositol trisphosphate (IP3) formation, whereas NECA did not. The effect of ATP on adenosine 3',5'-cyclic monophosphate (cAMP) but not on IP3 was abolished by a P1 antagonist, and such antagonists diminished its effect on secretion by as much as 75%. The potency orders of ATP analogues in increasing formation of cAMP and IP3 were different. The effects of the ATP analogues on phosphatidylcholine secretion were also inhibited by the P1 antagonists, with the greatest degree of inhibition being observed with the analogue that increased cAMP to the greatest extent. The effect of ATP on secretion was not diminished by either adenosine deaminase (previous data) or AMP deaminase showing that the effects of ATP were not mediated by its metabolism to the P1 agonists adenosine or AMP. These data show that ATP acts at both A2 and P2 receptors but that most of its effects on phosphatidylcholine secretion are mediated by the A2 receptor.
Griese
M
M
Department of Pediatrics, Yale University, School of Medicine, New Haven, Connecticut 06510.
Gobran
L I
LI
Rooney
S A
SA
D000659:AMP Deaminase / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D011983:Receptors, Purinergic; D013873:Thionucleotides; D014970:Xanthines; C030812:adenosine 5'-O-(2-thiodiphosphate); D019830:Adenosine-5'-(N-ethylcarboxamide); D000244:Adenosine Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000659:AMP Deaminase; D000241:Adenosine; D013726:Terbutaline