Physiological function and gene expression of adremnomedullinfamily : adrenal medullary cells and isolated blood vessels

1)肾上腺髓质素（AM）受体、降钙素基因相关肽（CGRP）受体和胰淀素受体分析：AM、CGRP和胰淀素在结构上同源，具有相似的生理功能。然而，这些肽的受体还没有得到很好的表征。我们研究了这些肽在少突胶质细胞KG 1C细胞的受体。KG 1C细胞表达钙调素受体样受体（CRLR）、受体活性调节蛋白（RAMP）-1、-2和-3。结果表明，-AM作用于AM受体（CRLR+RAMP-2，CRLR+RAMP-3）和CGRP 1受体（CRLR+RAMP-1），CGRP作用于CGRP 1受体和CGRP 2受体，胰淀素作用于CGRP 1受体。2）脑微血管和胶质细胞合成和分泌AM及其受体：脑微血管分泌AM至脑实质和血管腔侧，分泌至血管腔侧的AM水平比以往报道的高一个数量级。脑微血管AM分泌不明显， 关于我们 由凝血酶、脂多糖或细胞因子刺激的分泌物与外周血管内皮细胞的分泌物不同。然而，AM分泌到腔侧的刺激来自星形胶质细胞的可溶性因子。脑微血管内皮细胞和周细胞表达CRLR和RAMP-2和-3，AM刺激这些细胞产生cAMP。此外，我们还发现AM通过调节P-糖蛋白、胞饮和微血管紧密连接的完整性来激活血脑屏障功能。3）AM及其受体对妊娠的维持作用：CRLR和RAMP-1和-2在妊娠大鼠子宫中表达。AM在子宫附着胎盘部位的表达增加，而在非附着胎盘部位和绒毛膜中的表达不增加。胎盘所在的子宫条不自发收缩，但通过加入AM受体拮抗剂AM开始周期性收缩（22-52）。4）虹膜括约肌扩张机制：AM以自分泌/旁分泌方式作用于AM受体和CGRP 1受体，通过增加NO和cAMP水平扩张虹膜括约肌。少

1) Analysis of adrenomedullin (AM) receptors, calcitonin gene-related peptide (CGRP) receptors and amylin receptors :AM, CGRP and amylin are structurally homologus and they have similar physiological functions. However, receptors for these peptides have not well characterized. We studied receptors for these peptides in oligodendroglia KG1C cells. KG1C cells express caltitonin receptor-likereceptor (CRLR), receptor-activity-mocdifing protein (RAMP)-1, -2 and -3. We foundthat-AM acted on AM receptors (CRLR+RAMP-2, CRLR+RAMP-3) and CGRP1 receptors (CRLR+RAMP-1), CGRP acted on CGRP1 receptors and CGRP2 receptors, and amylin acted of CGRP1 receptors.2) Synthesis and secretion of AM and its receptors in brain microvessels and glial cells :Brain micovessels secreted AM into the brain parenchyma and the luminal side of the vessels, and the level of AM secreted to the luminal side of the vessels was one order higher than that reported previously. AM secretion from the brain microvessels was not … More stimulated by thrombin, lipopolysaccalide or cytokines differently form the secretion by the endotheial cells of peripheral vessels. However, the AM secretion to the luminal side was stimulated by the soluble factors derived from astrocytes. Endothelial cells and pericytes of brain microvessels expressde CRLR and RAMP-2 and -3, and AM stimulated CAMP production in these cells. In addition, we found that AM activated blood-brain barrier function by regulating p-glycoprotein, pinocytosis and integrity of tight junction of microvessels.3) Maintenance of pregnancy by AM and AM receptors :CRLR and RAMP-1 and -2 were expressed in the pregnant rat uterus. Expression of AM increased at the site of uterus attached to the placenta but not at the site not attached to the placenta or in the chorion. Uterus strip where the placenta was attached did not contract spontaneously, but began to contract periodically by the addition AM receptor antagonist, AM(22-52). These results suggest that AM and AM preceptors are involved in the maintenance of pregnancy by inhibiting the contraction of the uterus.4) Mechanism of dilatation of iris sphincter muscle :AM acted on AM preceptors and CGRP1 receptors in an autocrine/paracrine manner, and dilated the iris sphincter muscle by increasing NO and cAMP level. Less