Rubinstein I, Chandilawa R, Dagar S, Hong D, Gao X P
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
J Appl Physiol (1985). 2001 Aug;91(2):552-60. doi: 10.1152/jappl.2001.91.2.552.
The purpose of this study was to pharmacologically characterize the adenosine receptor subtype(s) that mediates adenosine-induced increases in macromolecular efflux from the intact hamster cheek pouch. Using intravital microscopy, we found that 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX), a selective adenosine receptor-1 antagonist, but not 3,7-dimethyl-1-propargylxanthine (DMPX), a selective adenosine receptor-2 antagonist, significantly attenuated adenosine-induced leaky site formation and increased clearance of fluorescein isothiocyanate-labeled dextran (molecular mass, 70 kDa) from the intact hamster cheek pouch (P < 0.05). Both compounds had no significant effects on bradykinin-induced responses. Nanomolar concentrations of R(-)-N(6)-(2-phenylisopropyl)-adenosine [R(-)-PIA], a selective adenosine A(1) agonist, evoked significant, concentration-dependent increases in macromolecular efflux. This response was significantly attenuated by PACPX but not by DMPX. In contrast, CGS-21680, a selective adenosine A(2) agonist, increased macromolecular efflux but only at micromolar concentrations. This response was significantly attenuated by DMPX but not by PACPX. Suffusion of nitroglycerin had no significant effects on R(-)-PIA- and CGS-21680-induced responses. In addition, suffusion of N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, had no significant effects on adenosine-induced responses. Indomethacin had no significant effects on adenosine-, R(-)-PIA-, and CGS-21680-induced increases in macromolecular efflux. Collectively, these data indicate that adenosine increases macromolecular efflux from the intact hamster cheek pouch by stimulating high-affinity adenosine A(1) receptors in a specific, nitric oxide- and prostaglandin-independent fashion.
本研究的目的是从药理学角度对介导腺苷诱导的大分子从完整的仓鼠颊囊流出增加的腺苷受体亚型进行表征。通过活体显微镜观察，我们发现，选择性腺苷A1受体拮抗剂1,3 - 二丙基 - 8 -（2 - 氨基 - 4 - 氯苯基）黄嘌呤（PACPX）能显著减弱腺苷诱导的渗漏部位形成，并增加异硫氰酸荧光素标记的葡聚糖（分子量70 kDa）从完整的仓鼠颊囊的清除率（P < 0.05），而选择性腺苷A2受体拮抗剂3,7 - 二甲基 - 1 - 炔丙基黄嘌呤（DMPX）则无此作用。这两种化合物对缓激肽诱导的反应均无显著影响。纳摩尔浓度的选择性腺苷A1激动剂R(-)-N(6)-(2 - 苯异丙基)-腺苷[R(-)-PIA]可引起大分子流出显著的、浓度依赖性增加。此反应被PACPX显著减弱，但未被DMPX减弱。相反，选择性腺苷A2激动剂CGS - 21680仅在微摩尔浓度时增加大分子流出。此反应被DMPX显著减弱，但未被PACPX减弱。灌注硝酸甘油对R(-)-PIA和CGS - 21680诱导的反应无显著影响。此外，一氧化氮合酶抑制剂N(G)-硝基 - L - 精氨酸甲酯灌注对腺苷诱导的反应无显著影响。吲哚美辛对腺苷、R(-)-PIA和CGS - 21680诱导的大分子流出增加无显著影响。总体而言，这些数据表明，腺苷通过以一种特定的、不依赖一氧化氮和前列腺素的方式刺激高亲和力腺苷A1受体，增加大分子从完整的仓鼠颊囊流出。
