Fluorescent ligand binding reveals heterogeneous distribution of adrenoceptors and 'cannabinoid-like' receptors in small arteries
Fluorescent ligand binding reveals heterogeneous distribution of adrenoceptors and 'cannabinoid-like' receptors in small arteries
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DOI：
10.1111/j.1476-5381.2009.00608.x
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发表时间：
2010-02-01
影响因子：
7.3
通讯作者：
McGrath, J. C.
中科院分区：
文献类型：
--
作者：
Daly, C. J.;Ross, R. A.;McGrath, J. C.
背景和目的：不同受体之间的协同作用或功能拮抗作用的药理学分析通常假设相互作用的受体位于相同的细胞中。实验方法：用荧光配体（α（1）-肾上腺素受体配体，BODIPY-FL-哌唑嗪，QAPB; β-肾上腺素受体配体，TMR-CGP 12177;荧光血管紧张素II;用共聚焦显微镜测量新的二芳基吡唑大麻素配体（Tocrifluor 1117，T1117）。小肠系膜和野生型和α（1B/D）-肾上腺素受体-KO小鼠的尾动脉被used.Key结果：T1117，大麻素CB 1受体拮抗剂AM 251的荧光形式，是GPR 55的配体，与CB 1受体的低亲和力。在肠系膜动脉平滑肌细胞中，α（1A）-肾上腺素受体主要位于与β-肾上腺素受体、血管紧张素受体或大麻素样（GPR 55）受体不同的细胞中。细胞与β-肾上腺素受体占主导地位的动脉分支。内皮细胞表达β-肾上腺素受体、α-肾上腺素受体和大麻素样受体。只有内皮α-肾上腺素受体出现在集群。外膜是G蛋白偶联受体（GPCRs）的丰富来源，特别是成纤维细胞和神经束，其中雪旺细胞结合α-肾上腺素受体，β-肾上腺素受体和CB受体配体，具有不同受体位置和共定位的混合物。在每种细胞类型内，每种GPCR具有独特的异质性分布，共定位有限，提供了一个指导的可能性，功能协同作用，并提出了一个新的范例协同作用，其中相互作用可能是细胞之间或涉及收敛细胞内信号传导过程。英国药理学杂志（2010）159，787-796; doi：10.1111/j.1476-5381.2009.00608.x; 2010年2月5日在线发表
Background and purpose: Pharmacological analysis of synergism or functional antagonism between different receptors commonly assumes that interacting receptors are located in the same cells. We have now investigated the distribution of alpha-adrenoceptors, beta-adrenoceptors and cannabinoid-like (GPR55) receptors in the mouse arteries.Experimental approach: Fluorescence intensity from vascular tissue incubated with fluorescent ligands (alpha(1)-adrenoceptor ligand, BODIPY-FL-prazosin, QAPB; beta-adrenoceptor ligand, TMR-CGP12177; fluorescent angiotensin II; a novel diarylpyrazole cannabinoid ligand (Tocrifluor 1117, T1117) was measured with confocal microscopy. Small mesenteric and tail arteries of wild-type and alpha(1B/D)-adrenoceptor-KO mice were used.Key results: T1117, a fluorescent form of the cannabinoid CB1 receptor antagonist AM251, was a ligand for GPR55, with low affinity for CB1 receptors. In mesenteric arterial smooth muscle cells, alpha(1A)-adrenoceptors were predominantly located in different cells from those with b-adrenoceptors, angiotensin receptors or cannabinoid-like (GPR55) receptors. Cells with beta-adrenoceptors predominated at arterial branches. Endothelial cells expressed beta-adrenoceptors, alpha-adrenoceptors and cannabinoid-like receptors. Only endothelial alpha-adrenoceptors appeared in clusters. Adventitia was a rich source of G protein-coupled receptors (GPCRs), particularly fibroblasts and nerve tracts, where Schwann cells bound alpha-adrenoceptor, beta-adrenoceptor and CB-receptor ligands, with a mix of separate receptor locations and co-localization.Conclusions and implications: Within each cell type, each GPCR had a distinctive heterogeneous distribution with limited co-localization, providing a guide to the possibilities for functional synergism, and suggesting a new paradigm for synergism in which interactions may be either between cells or involve converging intracellular signalling processes. British Journal of Pharmacology (2010) 159, 787-796; doi:10.1111/j.1476-5381.2009.00608.x; published online 5 February 2010