Dataset Information

The alpha 1B/D-adrenoceptor knockout mouse permits isolation of the vascular alpha 1A-adrenoceptor and elucidates its relationship to the other subtypes.

ABSTRACT:

Background and purpose

Mesenteric and carotid arteries from the alpha(1B/D)-adrenoceptor knockout (alpha(1B/D)-KO) were employed to isolate alpha(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 alpha(1)-adrenoceptor ligand BODIPY FL-Prazosin (QAPB), on mesenteric (an 'alpha(1A)-adrenoceptor' tissue) and carotid (an 'alpha(1D)-adrenoceptor' tissue) arteries.

Key results

Alpha(1B/D)-KO mesenteric arteries showed straightforward alpha(1A)-adrenoceptor agonist/antagonist pharmacology. WT had complex pharmacology with alpha(1A)- and alpha(1D)-adrenoceptor components. alpha(1B/D)-KO had a larger alpha(1A)-adrenoceptor response suggesting compensatory up-regulation: no increase in fluorescent ligand binding suggests up-regulation of signalling. alpha(1B/D)-KO carotid arteries had low efficacy alpha(1A)-adrenoceptor responses. WT had complex pharmacology consistent with co-activation of all three subtypes. Fluorescent binding had straightforward alpha(1A)-adrenoceptor characteristics in both arteries of alpha(1B/D)-KO. Fluorescent binding varied between cells in relative intracellular and surface distribution. Total fluorescence was reduced in the alpha(1B/D)-KO due to fewer smooth muscle cells showing fluorescent binding. WT binding was greater and sensitive to alpha(1A)- and alpha(1D)-adrenoceptor antagonists.

Conclusions and implications

The straightforward pharmacology and fluorescent binding in the alpha(1B/D)-KO was used to interpret the properties of the alpha(1A)-adrenoceptor in the WT. Reduced total fluorescence in alpha(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 alpha(1B/D)-KO suggesting different cellular phenotypes of alpha(1A)-adrenoceptor exist. The alpha(1B/D)-KO provides robust assays for the alpha(1A)-adrenoceptor and takes us closer to understanding multi-receptor subtype interactions.

SUBMITTER: Methven L

PROVIDER: S-EPMC2795267 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

The alpha 1B/D-adrenoceptor knockout mouse permits isolation of the vascular alpha 1A-adrenoceptor and elucidates its relationship to the other subtypes.

Methven L L McBride M M Wallace G A GA McGrath J C JC

British journal of pharmacology 20090630 1

<h4>Background and purpose</h4>Mesenteric and carotid arteries from the alpha(1B/D)-adrenoceptor knockout (alpha(1B/D)-KO) were employed to isolate alpha(1A)-adrenoceptor pharmacology and location and to reveal these features in the wild-type (WT) mouse.<h4>Experimental approach</h4>Functional pharmacology by wire myography and receptor localization by confocal microscopy, using the fluorescent alpha(1)-adrenoceptor ligand BODIPY FL-Prazosin (QAPB), on mesenteric (an 'alpha(1A)-adrenoceptor' tis ...[more]

PMID: 19572943

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Dataset Information

The alpha 1B/D-adrenoceptor knockout mouse permits isolation of the vascular alpha 1A-adrenoceptor and elucidates its relationship to the other subtypes.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

The alpha 1B/D-adrenoceptor knockout mouse permits isolation of the vascular alpha 1A-adrenoceptor and elucidates its relationship to the other subtypes.

Similar Datasets

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