Aiyar N, Baker E, Martin J, Patel A, Stadel J M, Willette R N, Barone F C
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
J Neurochem. 1995 Sep;65(3):1131-8. doi: 10.1046/j.1471-4159.1995.65031131.x.
Calcitonin gene-related peptide (CGRP), a 37-amino-acid peptide, is a member of a small family of peptides including amylin or islet amyloid polypeptide and salmon calcitonin. These related peptides have been shown to display similar effects on in vitro and in vivo carbohydrate metabolism. The present study was initiated to identify and characterize the binding sites for these peptides in lung and nucleus accumbens membranes prepared from pig and guinea pig. Both tissues in either species displayed high-affinity (2-[125I]iodohistidyl10)humanCGRP alpha ([125I]hCGRP alpha) binding (IC50 = 0.4-7.7 nM), which was displaced by hCGRP8-37 alpha with equally high affinity (IC50 = 0.4-7.3 nM). High-affinity binding for [125I]Bolton-Hunter human amylin ([125I]BH-h-amylin) was also observed in these tissues (IC50 = 0.2-6.0 nM). In membranes from the nucleus accumbens of both species, salmon calcitonin competed for amylin binding sites with high affinity (IC50 = 0.1 nM) but was poor in competing for amylin binding in lung membranes. Rat amylin8-37 competed for [125I]hCGRP alpha binding with higher affinity (IC50 = 5.4 nM) compared with [125I]BH-h-amylin binding (IC50 = 200 nM) in porcine nucleus accumbens, whereas in guinea pig nucleus accumbens, the IC50 values for rat amylin8-37 were 117 and 12 nM against [125I]hCGRP alpha and [125I]BH-h-amylin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
降钙素基因相关肽（CGRP）是一种由37个氨基酸组成的肽，是包括胰岛淀粉样多肽和鲑鱼降钙素在内的一个小肽家族的成员。这些相关肽已被证明在体外和体内碳水化合物代谢中表现出相似的作用。本研究旨在鉴定和表征这些肽在猪和豚鼠制备的肺和伏隔核膜中的结合位点。两种物种的这两种组织均显示出高亲和力（2-[125I]碘组氨酸10）人CGRPα（[125I]hCGRPα）结合（IC50 = 0.4 - 7.7 nM），其被hCGRP8 - 37α以同样高的亲和力取代（IC50 = 0.4 - 7.3 nM）。在这些组织中也观察到了对[125I]博尔顿 - 亨特人胰岛淀粉样多肽（[125I]BH - h - 胰岛淀粉样多肽）的高亲和力结合（IC50 = 0.2 - 6.0 nM）。在两种物种伏隔核的膜中，鲑鱼降钙素以高亲和力竞争胰岛淀粉样多肽结合位点（IC50 = 0.1 nM），但在肺膜中竞争胰岛淀粉样多肽结合的能力较差。在猪伏隔核中，大鼠胰岛淀粉样多肽8 - 37竞争[125I]hCGRPα结合的亲和力更高（IC50 = 5.4 nM），而竞争[125I]BH - h - 胰岛淀粉样多肽结合的亲和力较低（IC50 = 200 nM），而在豚鼠伏隔核中，大鼠胰岛淀粉样多肽8 - 37对[125I]hCGRPα和[125I]BH - h - 胰岛淀粉样多肽的IC50值分别为117和12 nM。（摘要截断于250字）
