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2-adrenergic
receptor subtype diversity: one receptor is not enough
Institut für Pharmakologie und Toxikologie, Universität Würzburg, 97078 Würzburg, Germany
2-Adrenergic receptors
mediate part of the diverse biological effects of the endogenous
catecholamines epinephrine and norepinephrine. Three distinct subtypes
of 2-adrenergic receptors, 2A,
2B, 2C, have been identified from
multiple species. Because of the lack of sufficiently subtype-selective
ligands, the specific biological functions of these receptor subtypes
were largely unknown until recently. Gene-targeted mice carrying
deletions in the genes encoding for individual
2-receptor subtypes have added important new insight into the physiological significance of adrenergic receptor diversity. Two different strategies have emerged to regulate adrenergic signal transduction. Some biological functions are controlled by two counteracting 2-receptor subtypes, e.g.,
2A-receptors decrease sympathetic outflow and blood
pressure, whereas the 2B-subtype increases blood
pressure. Other biological functions are regulated by synergistic
2-receptor subtypes. The inhibitory presynaptic feedback
loop that tightly regulates neurotransmitter release from adrenergic
nerves also requires two receptor subtypes, 2A and
2C. Similarly, nociception is controlled at several
levels by one of the three 2-receptor subtypes. Further
investigation of the specific function of 2-subtypes
will greatly enhance our understanding of the relevance of closely
related receptor proteins and point out novel therapeutic strategies
for subtype-selective drug development.
adrenergic receptors; transgenic mice; gene targeting
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