体内仓鼠颊囊微血管中胰淀素与降钙素基因相关肽受体的相互作用。

Interaction of amylin with calcitonin gene-related peptide receptors in the microvasculature of the hamster cheek pouch in vivo.

作者信息

Hall J M, Brain S D

机构信息

Pharmacology Group, School of Biological Sciences, University of Surrey, Guildford.

出版信息

Br J Pharmacol. 1999 Jan;126(1):280-4. doi: 10.1038/sj.bjp.0702272.

DOI:10.1038/sj.bjp.0702272

PMID:10051146

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565783/

Abstract

This study used intravital microscopy to investigate the receptors stimulated by amylin which shares around 50% sequence homology with the vasodilator calcitonin gene-related peptide (CGRP) in the hamster cheek pouch microvasculature in vivo. 2. Receptor agonists dilated arterioles (diameters 20-40 microm). The -log of the concentrations (+/- s.e.mean; n = 8) causing 50% increase in arteriole diameter were: human betaCGRP (10.8 +/- 0.3), human alphaCGRP (10.8 +/- 0.4), rat alphaCGRP (10.4 +/- 0.3). Rat amylin and the CGRP2 receptor selective agonist [Cys(ACM2,7]-human alphaCGRP were 100 fold less potent (estimates were 8.5 +/- 0.4 and 8.2 +/- 0.3 respectively). 3. The GCRP1 receptor antagonist, CGRP8-37 (300 nmol kg(-1); i.v.) reversibly inhibited the increase in diameter evoked by human alphaCGRP (0.3 nM) from 178 +/- 22% to 59 +/- 12% (n = 8; P < 0.05) and by rat amylin (100 nM) from 138 +/- 23% to 68 +/- 24% (n = 6; P < 0.05). CGRP8-37 did not inhibit vasodilation evoked by substance P (10 nM; n = 4: P > 0.05). 4. The amylin receptor antagonist, amylin8-37 (300 nmol kg(-1); i.v.) did not significantly inhibit the increase in diameter evoked by human alphaCGRP (0.3 nM) which was 112 +/- 26% in the absence, and 90 +/- 29% in the presence of antagonist (n = 4; P < 0.05); nor that evoked by rat amylin (100 nM) which was 146 +/- 23% in the absence and 144 +/- 32% in the presence of antagonist (n = 4; P > 0.05). 5. The agonist profile for vasodilatation and the inhibition of this dilatation by CGRP8-37, although not the amylin8-37 indicates that amylin causes vasodilatation through interaction with CGRP1 receptors in the hamster cheek pouch.

摘要

本研究采用活体显微镜技术，在体内观察仓鼠颊囊微血管系统中，与血管舒张剂降钙素基因相关肽（CGRP）具有约50%序列同源性的胰淀素所刺激的受体。2. 受体激动剂可使小动脉扩张（直径20 - 40微米）。引起小动脉直径增加50%的浓度的负对数（±标准误均值；n = 8）分别为：人βCGRP（10.8 ± 0.3）、人αCGRP（10.8 ± 0.4）、大鼠αCGRP（10.4 ± 0.3）。大鼠胰淀素和CGRP2受体选择性激动剂[Cys(ACM2,7]-人αCGRP的效力低100倍（估计分别为8.5 ± 0.4和8.2 ± 0.3）。3. GCRP1受体拮抗剂CGRP8 - 37（300 nmol kg⁻¹；静脉注射）可将人αCGRP（0.3 nM）引起的直径增加从178 ± 22%可逆性抑制至59 ± 12%（n = 8；P < 0.05），将大鼠胰淀素（100 nM）引起的直径增加从138 ± 23%抑制至68 ± 24%（n = 6；P < 0.05）。CGRP8 - 37未抑制P物质（10 nM；n = 4；P > 0.05）引起的血管舒张。4. 胰淀素受体拮抗剂胰淀素8 - 37（300 nmol kg⁻¹；静脉注射）未显著抑制人αCGRP（0.3 nM）引起的直径增加，无拮抗剂时为112 ± 26%，有拮抗剂时为90 ± 29%（n = 4；P < 0.05）；也未抑制大鼠胰淀素（100 nM）引起的直径增加，无拮抗剂时为146 ± 23%，有拮抗剂时为144 ± 3२%（n = 4；P > 0.05）。5. 血管舒张的激动剂图谱以及CGRP8 - 37对这种舒张的抑制作用（尽管胰淀素8 - 37无此作用）表明，胰淀素通过与仓鼠颊囊中的CGRP1受体相互作用引起血管舒张。