Background and purpose: Mesenteric and carotid arteries from the α_1B/D‐adrenoceptor knockout (α_1B/D‐KO) were employed to isolate α_1A‐adrenoceptor pharmacology and location and to reveal these features in the wild‐type (WT) mouse.Experimental approach: Functional pharmacology by wire myography and receptor localization by confocal microscopy, using the fluorescent α₁‐adrenoceptor ligand BODIPY FL‐Prazosin (QAPB), on mesenteric (an ‘α_1A‐adrenoceptor’ tissue) and carotid (an ‘α_1D‐adrenoceptor’ tissue) arteries.Key results: α_1B/D‐KO mesenteric arteries showed straightforward α_1A‐adrenoceptor agonist/antagonist pharmacology. WT had complex pharmacology with α_1A‐ and α_1D‐adrenoceptor components. α_1B/D‐KO had a larger α_1A‐adrenoceptor response suggesting compensatory up‐regulation: no increase in fluorescent ligand binding suggests up‐regulation of signalling. α_1B/D‐KO carotid arteries had low efficacy α_1A‐adrenoceptor responses. WT had complex pharmacology consistent with co‐activation of all three subtypes. Fluorescent binding had straightforward α_1A‐adrenoceptor characteristics in both arteries of α_1B/D‐KO. Fluorescent binding varied between cells in relative intracellular and surface distribution. Total fluorescence was reduced in the α_1B/D‐KO due to fewer smooth muscle cells showing fluorescent binding. WT binding was greater and sensitive to α_1A‐ and α_1D‐adrenoceptor antagonists.Conclusions and implications: The straightforward pharmacology and fluorescent binding in the α_1B/D‐KO was used to interpret the properties of the α_1A‐adrenoceptor in the WT. Reduced total fluorescence in α_1B/D‐KO arteries, despite a clear difference in the functionally dominant subtype, indicates that measurement of receptor protein is unlikely to correlate with function. Fewer cells bound QAPB in the α_1B/D‐KO suggesting different cellular phenotypes of α_1A‐adrenoceptor exist. The α_1B/D‐KO provides robust assays for the α_1A‐adrenoceptor and takes us closer to understanding multi‐receptor subtype interactions.

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