Beach R E, Good D W
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Am J Physiol. 1992 Sep;263(3 Pt 2):F482-7. doi: 10.1152/ajprenal.1992.263.3.F482.
Previously, we demonstrated that adenosine (Ado) was released by the medullary thick ascending limb (MTAL) during hypoxia. The present experiments were designed to examine the effects of Ado and adenosine analogues on net chloride (JCl) and bicarbonate (JHCO3) absorption by the isolated, perfused MTAL of the rat. Ado, 10 nM, in the presence or absence of arginine vasopressin (AVP, 10(-10) M) reduced JCl by 50%. The inhibition of Ado was reproduced with the selective A1 agonist, N-6-phenylisopropyladenine (2 nM), and was reversed by 8-cyclopentyl-1,3-dipropylxanthine, an A1-receptor antagonist. Thus the inhibition of JCl is likely mediated through A1 receptors. In contrast, Ado had no effect on (JHCO3) either in the presence or absence of AVP. Ado also had no influence on the effect of AVP to inhibit JHCO3. The lack of effect on JHCO3 suggests that the inhibition of JCl by Ado is unlikely to be mediated through changes in cellular adenosine 3',5'-cyclic monophosphate. These results support the hypothesis that Ado released into the renal medulla during hypoxia may protect the MTAL from ischemic injury by directly inhibiting NaCl absorption and reducing transport-related oxygen consumption.
此前，我们证明了在缺氧期间延髓髓袢升支粗段（MTAL）会释放腺苷（Ado）。本实验旨在研究Ado及腺苷类似物对大鼠离体灌注MTAL净氯化物（JCl）和碳酸氢盐（JHCO3）吸收的影响。10 nM的Ado在有或无精氨酸加压素（AVP，10^(-10) M）存在的情况下可使JCl降低50%。选择性A1激动剂N-6-苯基异丙基腺苷（2 nM）可重现Ado的抑制作用，且A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤可逆转该抑制作用。因此，JCl的抑制可能是通过A1受体介导的。相比之下，无论有无AVP，Ado对（JHCO3）均无影响。Ado对AVP抑制JHCO3的作用也无影响。对JHCO3无作用表明Ado对JCl的抑制不太可能是通过细胞内3',5'-环磷酸腺苷的变化介导的。这些结果支持了以下假说：缺氧期间释放到肾髓质中的Ado可能通过直接抑制NaCl吸收和减少与转运相关的氧消耗来保护MTAL免受缺血性损伤。
