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Endocrine Abstracts (2006) 11 S35

1University of Freiburg, Freiburg, Germany; 2University of Wuerzburg, Wuerzburg, Germany.

The family of adrenergic receptors contains nine different subtypes of G protein-coupled receptors which mediate the biological effects of adrenaline and noradrenaline. With few exceptions, the full therapeutic potential of subtype-selective therapy has not yet been explored for the group of adrenergic receptors. In the absence of sufficiently subtype-selective ligands which can distinguish between individual receptor subtypes of the adrenergic family, gene-targeted mouse models with deletions in these receptor genes have recently been generated and characterized. These genetic mouse models have helped to assign specific pharmacological effects of alpha2-receptor agonists or antagonists to individual receptor subtypes.

Some unexpected and novel functions of alpha2-adrenergic receptors were also uncovered in these mouse models: Presynaptic control of catecholamine release from adrenergic nerves in the central and sympathetic nervous system is regulated by all three different receptor subtypes, alpha2A, alpha2B, and alpha2C. A similar feedback loop also controls the release of catecholamines from the adrenal gland. Alpha2B-receptors are not only involved in regulating vascular tone in the adult organism, but they are essential for the development of the vascular system of the placenta during prenatal development and for angiogensis in the adult organism. In humans, genetic diversity of the adrenoceptor genes has been intensely studied recently. Among the alpha2-adrenoceptors, a hypofunctional deletion variant of the alpha2C-receptor has been associated with altered disease progression in patients with chronic heart failure. The challenge will now be to translate the results from subtype-selective gene deletions in mice into clinical science and to predict the action of subtype-selective drugs in humans.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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