Marone G, Petracca R, Vigorita S, Casolaro V
Department of Medicine, University of Naples Federico II, II School of Medicine, Italy.
Biochem Pharmacol. 1990 Nov 1;40(9):1963-73. doi: 10.1016/0006-2952(90)90225-a.
We have investigated the effects of 2',5'-dideoxyadenosine (DDA), 9'-beta-D-arabinofuranosyladenine (ARA), and 9-beta-D-xylofuranosyladenine (XFA), which have been classified as P-site adenosine agonists, on the cyclic adenosine 3',5'-monophosphate (cAMP) metabolism of human lymphocytes and polymorphonuclear leukocytes (PMNs). DDA (10(-5)-2 x 10(-4) M), ARA and XFA caused a dose-dependent decrease in cAMP content of human lymphocytes. In addition to decreasing lymphocyte cAMP levels, DDA, ARA, and XFA markedly inhibited the effects of many adenylate cyclase-stimulating agents including beta-adrenergic stimuli, prostaglandin E1 (PGE1), histamine, adenosine, forskolin and cholera toxin. Theophylline and 3-isobutyl-1-methylxanthine, which are known antagonists of adenosine A1/Ri and A2/Ra receptors, did not modify the inhibiting effects of DDA. Mn2+ (1 mM) increased the sensitivity to inhibition of adenylate cyclase agonists by DDA. We also search for the presence of adenosine P-sites in human PMNs. DDA caused a significant decrease of PMN cAMP levels only at the highest concentrations used (2 x 10(-4) M). In contrast, even low concentrations of DDA (10(-6)-10(-4) M) concentration-dependently blocked the stimulatory effect of PGE1 and forskolin on PMN cAMP accumulation. The results support the existence of a purine P-site that regulates cAMP metabolism of human lymphocytes and PMNs.
我们研究了已被归类为P位点腺苷激动剂的2',5'-二脱氧腺苷（DDA）、9'-β-D-阿拉伯呋喃糖基腺嘌呤（ARA）和9-β-D-木糖呋喃糖基腺嘌呤（XFA）对人淋巴细胞和多形核白细胞（PMN）中环磷酸腺苷（cAMP）代谢的影响。DDA（10^(-5)-2×10^(-4) M）、ARA和XFA导致人淋巴细胞cAMP含量呈剂量依赖性下降。除了降低淋巴细胞cAMP水平外，DDA、ARA和XFA还显著抑制了许多腺苷酸环化酶刺激剂的作用，包括β-肾上腺素能刺激剂、前列腺素E1（PGE1）、组胺、腺苷、福斯高林和霍乱毒素。茶碱和3-异丁基-1-甲基黄嘌呤是已知的腺苷A1/Ri和A2/Ra受体拮抗剂，它们并未改变DDA的抑制作用。Mn2+（1 mM）增加了DDA对腺苷酸环化酶激动剂抑制作用的敏感性。我们还研究了人PMN中腺苷P位点的存在情况。仅在所用的最高浓度（2×10^(-4) M）下，DDA才导致PMN cAMP水平显著下降。相比之下，即使是低浓度的DDA（10^(-6)-10^(-4) M）也能浓度依赖性地阻断PGE1和福斯高林对PMN cAMP积累的刺激作用。这些结果支持存在一个调节人淋巴细胞和PMN中cAMP代谢的嘌呤P位点。
