降钙素基因相关肽（CGRP）受体拮抗剂CGRP（8-37）对滑膜血流的调节作用

Modulation of synovial blood flow by the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8-37).

作者信息

McMurdo L, Lockhart J C, Ferrell W R

机构信息

Institute of Biomedical & Life Sciences, University of Glasgow.

出版信息

Br J Pharmacol. 1997 Jul;121(6):1075-80. doi: 10.1038/sj.bjp.0701237.

DOI:10.1038/sj.bjp.0701237

PMID:9249241

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564796/

Abstract

The effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8-37) on blood flow in the knee joint of the anaesthetized rat was investigated. 2. Synovial blood flow in both exposed and intact, skin-covered knees was measured by laser Doppler perfusion imaging. 3. Topical application of CGRP(8-37) caused a dose-dependent fall in synovial blood flow in the exposed knee joint of the rat. At low (1.5 nmol) doses of CGRP(8-37) there was no significant effect on synovial blood flow. In rats treated with 7.5 nmol CGRP(8-37) there was a fall in synovial blood flow (maximum effect at 10 min: -28.8 +/- 4.6%; n=7), which returned to resting levels within 30 min. The highest dose (15 nmol) of antagonist used in this study caused a marked (maximum at 10 min: -35.6 +/- 9.3%; n=8), and prolonged (up to 30 min) fall in blood flow. 4. Ten days after surgical denervation, CGRP(9-37) (15 nmol, topical) had no significant effect on blood flow in the rat exposed knee joint (change in flux at 10 min: -5.1+/-3.6%; n=4). This suggests that CGRP(8-37) acts selectively to antagonize the actions of a neurally derived product, probably CGRP, on the rat synovial vasculature. 5. In skin-covered knee joints, intra-articular injection of CGRP(8-37) (15 nmol; bolus) elicited a significant fall in synovial blood flow (maximum effect at 10 min: -15.5 +/- 5.8%; n=6). 6. CGRP (0.01, 0.1 or 1.0 nmol; topical) caused a dose-dependent increase in exposed knee joint blood flow, which was attenuated by co-administration of 1.5 nmol CGRP(8-37). For example, 1 nmol CGRP elicited a peak increase in flux at 10 min of 94.7 +/- 31.8% (n=8) and 28.8 +/- 8.9% (n=7) in the absence and presence of CGRP(8-37), respectively. The vasodilator responses induced by acetylcholine (ACh) (10 nmol, topical; n=4-5) or sodium nitroprusside (SNP) (10 nmol, topical; n=4-5) were unaltered in the presence of CGRP(8-37) (1.5 nmol, topical). 7. Thus, the CGRP receptor antagonist CGRP(8-37) elicits vasoconstriction in the rat synovium. This suggests that the endogenous, basal release of CGRP may play a physiological role in the regulation of blood flow in the rat knee joint.

摘要

研究了降钙素基因相关肽（CGRP）受体拮抗剂CGRP（8 - 37）对麻醉大鼠膝关节血流的影响。2. 通过激光多普勒灌注成像测量暴露的和完整的、有皮肤覆盖的膝关节的滑膜血流。3. 局部应用CGRP（8 - 37）导致大鼠暴露膝关节的滑膜血流呈剂量依赖性下降。低剂量（1.5 nmol）的CGRP（8 - 37）对滑膜血流无显著影响。用7.5 nmol CGRP（8 - 37）处理的大鼠，滑膜血流下降（10分钟时最大效应：-28.8±4.6%；n = 7），30分钟内恢复到静息水平。本研究中使用的最高剂量（15 nmol）拮抗剂导致血流显著下降（10分钟时最大效应：-35.6±9.3%；n = 8），且持续时间延长（长达30分钟）。4. 手术去神经10天后，CGRP（9 - 37）（15 nmol，局部应用）对大鼠暴露膝关节的血流无显著影响（10分钟时通量变化：-5.1±3.6%；n = 4）。这表明CGRP（8 - 37）选择性地拮抗神经源性产物（可能是CGRP）对大鼠滑膜血管系统的作用。5. 在有皮肤覆盖的膝关节中，关节内注射CGRP（8 - 37）（15 nmol；推注）引起滑膜血流显著下降（10分钟时最大效应：-15.5±5.8%；n = 6）。6. CGRP（0.01、0.1或1.0 nmol；局部应用）导致暴露膝关节血流呈剂量依赖性增加，联合应用1.5 nmol CGRP（8 - 37）可使其减弱。例如，1 nmol CGRP在不存在和存在CGRP（8 - 37）时，10分钟时通量峰值增加分别为94.7±31.8%（n = 8）和28.8±8.9%（n = 7）。在存在CGRP（8 - 37）（1.