Adenosine A1 receptor-mediated inhibition of surfactant secretion in rat type II pneumocytes.
Phosphatidylcholine secretion in type II pneumocytes has been reported to be stimulated by P1 and P2 purinoceptor agonists. P1 receptors are divided into A1 and A2 subtypes with opposite effects on the levels of adenosine 3',5'-cyclic monophosphate (cAMP). Stimulated secretion in type II cells is mediated by the A2 receptor and accompanied by an increase in cAMP concentration. We now report evidence suggesting the existence of an A1 receptor-inhibiting secretion in type II cells from adult rats. The rate of phosphatidylcholine secretion was approximately doubled by 5'(N-ethylcarboxyamido) adenosine (NECA), terbutaline, and forskolin, all of which increase cAMP levels. Adenosine deaminase increased the stimulatory effect of these agonists to approximately three-fold but it had not effect on secretion stimulated by agonists which do not increase cAMP levels. The effect of adenosine deaminase on terbutaline-stimulated secretion was antagonized by selective adenosine A1 receptor agonists, N6-cyclopentyladenosine (CPA) and 1-deaza-2-chloro-N6-cyclopentyladenosine (DCCA). The maximum inhibitory effects of CPA and DCCA were achieved at 10(-9) M and 10(-11) M, respectively. At these concentrations CPA and DCCA had no effect on the rate of basal secretion or on terbutaline-stimulated secretion in the absence of adenosine deaminase. We suggest that adenosine deaminase stimulates phosphatidylcholine secretion by removing adenosine that occupies A1 receptors, thus reversing inhibition of cAMP-mediated secretion.
Gobran
L I
LI
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Rooney
S A
SA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013726:Terbutaline / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D010713:Phosphatidylcholines; D011983:Receptors, Purinergic; C044295:1,2-dioctanoylglycerol; C063165:1-deaza-2-chloro-N(6)-cyclopentyladenosine; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; D015759:Ionomycin; D000255:Adenosine Triphosphate; D000241:Adenosine; D013726:Terbutaline; D002794:Choline; D013755:Tetradecanoylphorbol Acetate