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的GTP结合蛋白(GI)在外周小动脉α2-肾上腺素能受体(AR)信号转导系统中的作用。术后4周，从提睾肌中分离出小动脉(Phi100um)，两端植入玻璃微针，在组织浴中用Krebs液灌流。我们观察了百日咳毒素(PTX)给药前后小动脉对α2激动剂(UK-14,304：UK)和ATP敏感性钾通道(K&lt；ATP&gt；)拮抗剂(格列本脲：GLB)的反应。PTX给药后对UK的浓度-反应曲线(CRC)受到抑制，但CRCs对GLB的反应没有改变。我们的数据表明，Gi蛋白可能在α2-AR和K_&lt；ATP&gt；之间传递信号。这项研究的第二个目标是测试酸中毒导致α2微动脉收缩的机制。在UK同时刺激α2-AR的过程中，GLB所产生的CRC被完全消除，但通过同时激活K&lt；ATP和Gt；酸中毒，这种CRC完全恢复。这些结果提示，酸中毒是开放K_1；ATP&Gt；的一种现象，这一现象是α_2微动脉收缩时酸性抑制的主要原因。

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.