Signal transduction system of alpha 2-adrenoceptor and its inhibition by acidosis.

本研究的第一个目的是阐明百日咳毒素敏感性GTP结合蛋白（Gi）在外周小动脉α_2-肾上腺素能受体（AR）信号转导系统中的作用。术后4周，从提睾肌处切取小动脉（φ 100 μ m），两端插入玻璃微吸管，组织浴中Krebs液灌注。我们观察了百日咳毒素（PTX）给药前和给药后小动脉对α 2受体激动剂（UK-14，304：UK）和ATP敏感性K^+通道（K ^+<ATP>）拮抗剂（格列本脲：GLB）的反应。结果表明，Gi蛋白可能是α_2-AR与K_1之间的信号传递蛋白<ATP>。本研究的第二个目的是测试酸中毒抑制α 2小动脉收缩的机制。用UK刺激α_2-AR可使GLB诱导的CRC消失，而同时激活α_2-AR和K_2酸中毒则可使CRC完全恢复<ATP>。结果提示，<ATP>酸中毒引起K_2开放，这是α_2微动脉收缩受酸抑制的主要原因。

The first aim of this study is to clarify the role of pertussis-toxin sensitive GTP-binding protein (Gi) on alpha2-adrenoceptor (AR) signal transduction system in the peripheral arteriole. An arteriole (phi100um) was dissected out from the cremaster and was inserted glass micropippettes from both ends, and was perfused by Krebs solution in tissue bath 4 weeks after operation. We evaluated responses in the arterioles to alpha2-agonists (UK-14,304 : UK) and ATP-sensitive K^+-channel (K_<ATP>) antagonist (glibenclamide : GLB) before anf after pertussis-toxin (PTX) administration.Concentration-response curves (CRC) to UK were inhibited, but CRCs to GLB were not changed after PTX administration. Our data shows that Gi-protein may transmit the signal between alpha2-AR and K_<ATP>. The second goal of this study is to test the mechanism of the inbition of alpha2 arteriole constriction by acidosis. The CRC by GLB was abolished during by concomitant alpha2-AR stimulation by UK,but this CRC was completely restored by simultaneous activation of with K_<ATP> acidosis. Thses findings suggest that K_<ATP> is opened by acidosis and this phenomenone is main reason of acidic inhibition in alpha2 arteriole constriction.