EFFECTS OF ADENOSINE ON ION-TRANSPORT IN RAT MEDULLARY THICK ASCENDING LIMB

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 (J(Cl)) and bicarbonate (J(HCO3)) 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 J(Cl) by 50%. The inhibition by Ado was reproduced with the selective Al agonist, N-6-phenylisopropyladenine (2 nM), and was reversed by 8-cyclopentyl-1,3-dipropylxanthine, an A1-receptor antagonist. Thus the inhibition of J(Cl) is likely mediated through A, receptors. In contrast, Ado had no effect on (J(HCO3)) either in the presence or absence of AVP. Ado also had no influence on the effect of AVP to inhibit J(HCO3). The lack of effect on J(HCO3) suggests that the inhibition of J(Cl) 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.