Adenosine stimulates nitric oxide synthesis in rat cardiac myocytes.
We investigated the effects of adenosine on nitric oxide (NO) synthesis by measuring the production of nitrite, a stable metabolite of NO, in cultured neonatal rat cardiac myocytes. Incubation of cultures with interleukin-1 beta (10 ng/ml) for 24 h caused a significant increase in nitrite production. The interleukin-1 beta-induced nitrite production by cardiac myocytes was significantly increased by adenosine or its stable analog 2-chloroadenosine in a dose-dependent manner (10(-7)-10(-4) M). The adenosine A2-receptor antagonist KF-17837 (10(-6) M), but not the A1-receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (10(-6) M), significantly inhibited 2-chloroadenosine-mediated nitrite production. The 2-chloroadenosine-induced nitrite production by interleukin-1 beta-stimulated cells was accompanied by inducible NO synthase mRNA and protein accumulation. In the presence of N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (cAMP) (10(-3) M) or isoproterenol (10(-5) M), interleukin-1 beta-induced nitrite accumulation was further increased, but the effect of 2-chloroadenosine was not additive or synergistic. The protein kinase C inhibitor calphostin C did not inhibit the effect of 2-chloroadenosine. These results indicate that adenosine acts on A2 receptors and augments NO synthesis in interleukin-1 beta-stimulated cardiac myocytes, at least partially through a cAMP-dependent pathway.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Kurosaki
K
K
Shimpo
M
M
Okada
K
K
Saito
T
T
Shimada
K
K
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000032:analysis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013237:Stereoisomerism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D009281:Naphthalenes; D009573:Nitrites; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011994:Recombinant Proteins; D014970:Xanthines; D015762:2-Chloroadenosine; C081198:KF 17837; D003609:Dactinomycin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C053907:8-cyclopentyl-1,3-dimethylxanthine; D003994:Bucladesine; D013806:Theophylline; D011493:Protein Kinase C; C058819:calphostin C; D000241:Adenosine; D007545:Isoproterenol