ucn-1028-c and 8-cyclopentyl-1-3-dimethylxanthine

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.

Topics: 2-Chloroadenosine; Adenosine; Animals; Animals, Newborn; Bucladesine; Cells, Cultured; Dactinomycin; Enzyme Inhibitors; Heart; Humans; Interleukin-1; Isoproterenol; Myocardium; Naphthalenes; Nitric Oxide; Nitrites; omega-N-Methylarginine; Protein Kinase C; Purinergic P1 Receptor Antagonists; Purinergic P2 Receptor Antagonists; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stereoisomerism; Theophylline; Xanthines