Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1146-52. doi: 10.1152/ajpheart.00301.2010. Epub 2010 Jul 9.
Erythrocytes release ATP in response to exposure to the physiological stimulus of lowered oxygen (O(2)) tension as well as pharmacological activation of the prostacyclin receptor (IPR). ATP release in response to these stimuli requires activation of adenylyl cyclase, accumulation of cAMP, and activation of protein kinase A. The mechanism by which ATP, a highly charged anion, exits the erythrocyte in response to lowered O(2) tension or receptor-mediated IPR activation by iloprost is unknown. It was demonstrated previously that inhibiting pannexin 1 with carbenoxolone inhibits hypotonically induced ATP release from human erythrocytes. Here we demonstrate that three structurally dissimilar compounds known to inhibit pannexin 1 prevent ATP release in response to lowered O(2) tension but not to iloprost-induced ATP release. These results suggest that pannexin 1 is the conduit for ATP release from erythrocytes in response to lowered O(2) tension. However, the identity of the conduit for iloprost-induced ATP release remains unknown.
红细胞在暴露于低氧（O2）张力的生理刺激以及前列腺素 I2 受体（IPR）的药理学激活下会释放 ATP。这些刺激引起的 ATP 释放需要激活腺苷酸环化酶、cAMP 积累和蛋白激酶 A 的激活。ATP 是一种带高电荷的阴离子，在响应低氧张力或由伊洛前列素介导的 IPR 激活时从红细胞中释放的机制尚不清楚。先前已经证明，用 carbenoxolone 抑制连接蛋白 1 可抑制人红细胞在低渗诱导下释放 ATP。在这里，我们证明三种结构不同的已知可抑制连接蛋白 1 的化合物可阻止对低氧张力的反应而不阻止伊洛前列素诱导的 ATP 释放。这些结果表明，连接蛋白 1 是红细胞对低氧张力反应时释放 ATP 的通道。然而，伊洛前列素诱导的 ATP 释放的通道仍然未知。
