Which vascular cells have adrenoceptors

Blood vessels are believed to be constricted and/or dilated by catecholamines via agonism at α- or β-adrenoceptors (AR), respectively, located on smooth muscle. However, other cell types may be involved in moderating vascular responses to catecholamines or surrogate “selective” agonists (e.g. endothelium, adventitial cells and adipose tissue). It is not always clear whether this is due to constitutive activity of the other cell types or to a direct action of catecholamines at adrenoceptors on these other cells. In addition, signalling from smooth muscle cells could be transmitted to other cell types via gap junctions. It would be useful to know where exactly adrenoceptors are located in blood vessels. As an approach to this issue we have examined the distribution of adrenoceptors on various cell types of small resistance arteries using fluorescent ligands or GFP-labelled receptors. Methods: Arteries of various sizes were dissected from male mice or rats and examined either with or without fixation by confocal microscopy. Adrenoceptors were rendered visible by fluorescent antagonist ligands or by employing strains of mice harbouring transgenic adrenoceptors labelled with green fluorescent protein. Results: The β-AR-selective fluorescent ligand BODIPY TMR-CGP 12177 and the α1-adrenoceptor ligand BODIPY-FL-PRAZOSIN (QAPB) both bound to cells in all three vascular coats, including endothelial cells, medial smooth muscle cells and a variety of adventitial cell types including fibroblasts and nerve-like cells with long processes. Specificity of binding was confirmed with the irreversible antagonists BAAM and phenoxybenzamine, respectively. The binding was uneven between individual cells and when co-localisation of α1- and β-AR was sought using different coloured labels a range of phenotypes emerged that harboured one or other or both types of receptor. In transgenic mice harbouring GFP-labelled α1a- or α1b-AR fluorescence was detected in smooth muscle cells; this was more evenly distributed for α1b- than for α1a-AR. Conclusion: This study shows that the location of adrenoceptors in blood vessels extends to several other cell types beyond smooth muscle and has many interesting implications for our understanding of vascular regulation by catecholamines.