Fluorescent ligand binding reveals heterogeneous distribution of adrenoceptors and ‘cannabinoid-like’ receptors in small arteries

Daly, C.J., Ross, R.A., Whyte, J., Henstridge, C.M., Irving, A.J. and McGrath, J.C. (2010) Fluorescent ligand binding reveals heterogeneous distribution of adrenoceptors and ‘cannabinoid-like’ receptors in small arteries. British Journal of Pharmacology, 159(4), pp. 787-796. (doi:10.1111/j.1476-5381.2009.00608.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1476-5381.2009.00608.x

Abstract

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 a-adrenoceptors, ß-adrenoceptors and cannabinoid-like (GPR55) receptors in the mouse arteries.Experimental approach: Fluorescence intensity from vascular tissue incubated with fluorescent ligands (a1-adrenoceptor ligand, BODIPY-FL-prazosin, QAPB; ß-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 a1B/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, a1A-adrenoceptors were predominantly located in different cells from those with ß-adrenoceptors, angiotensin receptors or cannabinoid-like (GPR55) receptors. Cells with ß-adrenoceptors predominated at arterial branches. Endothelial cells expressed ß-adrenoceptors, a-adrenoceptors and cannabinoid-like receptors. Only endothelial a-adrenoceptors appeared in clusters. Adventitia was a rich source of G protein-coupled receptors (GPCRs), particularly fibroblasts and nerve tracts, where Schwann cells bound a-adrenoceptor, ß-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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Daly, Dr Craig and McGrath, Professor Ian
Authors: Daly, C.J., Ross, R.A., Whyte, J., Henstridge, C.M., Irving, A.J., and McGrath, J.C.
Subjects:Q Science > Q Science (General)
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:British Journal of Pharmacology
ISSN:0007-1188
ISSN (Online):1476-5381
Published Online:05 February 2010

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