Wookey P J, Tikellis C, Du H C, Qin H F, Sexton P M, Cooper M E
Department of Medicine, University of Melbourne, Victoria, Australia.
Am J Physiol. 1996 Feb;270(2 Pt 2):F289-94. doi: 10.1152/ajprenal.1996.270.2.F289.
125I-labeled rat amylin binds to specific sites in the cortex of rat kidney, which can be distinguished from those for 125I-labeled salmon calcitonin (sCT) and 125I-labeled rat alpha-calcitonin gene-related peptide (alpha-CGRP) on the basis of regional distribution. These sites have a high affinity (approximately 1 nM) for amylin, and 125I-amylin binding is potently inhibited by the peptide antagonists AC413 and sCT-(8-32), whereas CGRP-(8-37) is a poor inhibitor of binding. Furthermore, incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibits 125I-amylin binding by > 90%, indicating that binding is dependent on coupling to G proteins. In renal cortex, amylin stimulated adenylyl cyclase activity three- to fourfold, and this was inhibited by AC413 and sCT-(8-32) but not by CGRP-(8-37). Amylin activated plasma renin twofold, and this was blunted by prior administration of AC413 but not CGRP-(8-37). We speculate that amylin may play an important role in renal physiology and that in states of hyperamylinemia, as found in obesity and the insulin resistance syndrome, this peptide may be involved in the genesis and development of hypertension.
125I标记的大鼠胰岛淀粉样多肽可与大鼠肾皮质中的特异性位点结合，根据区域分布情况，这些位点可与125I标记的鲑鱼降钙素（sCT）及125I标记的大鼠α-降钙素基因相关肽（α-CGRP）的结合位点区分开来。这些位点对胰岛淀粉样多肽具有高亲和力（约1 nM），肽拮抗剂AC413和sCT-(8-32)可有效抑制125I-胰岛淀粉样多肽的结合，而CGRP-(8-37)对结合的抑制作用较弱。此外，用鸟苷5'-O-(3-硫代三磷酸)（GTPγS）孵育可使125I-胰岛淀粉样多肽的结合减少>90%，表明这种结合依赖于与G蛋白的偶联。在肾皮质中，胰岛淀粉样多肽可使腺苷酸环化酶活性增加三到四倍，AC413和sCT-(8-32)可抑制这一作用，但CGRP-(8-37)则无此作用。胰岛淀粉样多肽可使血浆肾素活性增加两倍，预先给予AC413可减弱这一作用，但CGRP-(8-37)则无此作用。我们推测，胰岛淀粉样多肽可能在肾脏生理过程中发挥重要作用，在肥胖和胰岛素抵抗综合征等高胰岛淀粉样多肽血症状态下，该肽可能参与高血压的发生和发展。
