豚鼠输精管上降钙素基因相关肽和肾上腺髓质素受体的特性研究

Characterization of receptors for calcitonin gene-related peptide and adrenomedullin on the guinea-pig vas deferens.

作者信息

Poyner D R, Taylor G M, Tomlinson A E, Richardson A G, Smith D M

机构信息

Pharmaceutical Sciences Institute, Aston University, Birmingham, England.

出版信息

Br J Pharmacol. 1999 Mar;126(5):1276-82. doi: 10.1038/sj.bjp.0702437.

DOI:10.1038/sj.bjp.0702437

PMID:10205019

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565898/

Abstract

The receptors which mediate the effects of calcitonin gene-related peptide (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been investigated. 2. All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD2s for CGRP, amylin and adrenomedullin of 7.90+/-0.11, 7.70+/-0.19 and 7.25+/-0.10 respectively). 3. CGRP8-37 (1 microM) and AC187 (10 microM) showed little antagonist activity against adrenomedullin. 4. Adrenomedullin22-52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5. [125I]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC50 of 8.91 and a capacity of 643 fmol mg(-1). Its selectivity profile was adrenomedullin> AC187>CGRP=amylin. It was clearly distinct from a site labelled by [125I]-CGRP (pIC50=8.73, capacity=114 fmol mg(-1), selectivity CGRP>amylin=AC187>adrenomedullin). [125I]-amylin bound to two sites with a total capacity of 882 fmol mg(-1). 6. Although CGRP has been shown to act at a CGRP2 receptor on the vas deferens with low sensitivity to CGRP8-37, this antagonist displaced [125I]-CGRP with high affinity from vas deferens membranes. This affinity was unaltered by increasing the temperature from 4 degrees C to 25 degrees C, suggesting the anomalous behaviour of CGRP8-37 is not due to temperature differences between binding and functional assays.

摘要

对介导降钙素基因相关肽（CGRP）、胰淀素和肾上腺髓质素对豚鼠输精管作用的受体进行了研究。2. 所有这三种肽均引起电刺激抽搐反应的浓度依赖性抑制（CGRP、胰淀素和肾上腺髓质素的pD2分别为7.90±0.11、7.70±0.19和7.25±0.10）。3. CGRP8 - 37（1微摩尔）和AC187（10微摩尔）对肾上腺髓质素几乎没有拮抗活性。4. 肾上腺髓质素22 - 52本身可抑制输精管的电刺激收缩，并且还能拮抗对CGRP、胰淀素和肾上腺髓质素的反应。5. [125I] - 肾上腺髓质素标记了输精管膜中单一的结合位点群体，其pIC50为8.91，容量为643飞摩尔/毫克（-1）。其选择性概况为肾上腺髓质素>AC187>CGRP = 胰淀素。它明显不同于由[125I] - CGRP标记的位点（pIC50 = 8.73，容量 = 114飞摩尔/毫克（-1），选择性CGRP>胰淀素 = AC187>肾上腺髓质素）。[125I] - 胰淀素结合到两个位点，总容量为882飞摩尔/毫克（-1）。6. 尽管已证明CGRP作用于输精管上对CGRP8 - 37敏感性较低的CGRP2受体，但这种拮抗剂以高亲和力从输精管膜上置换[125I] - CGRP。将温度从4℃升高到25℃时，这种亲和力未改变，表明CGRP8 - 37的异常行为并非由于结合试验和功能试验之间的温度差异所致。