Аннотация
Although G protein-coupled receptor-mediated signaling is one of the
best studied biological events, little is known about the kinetics
of these processes in intact cells. Experiments with neurons from
alpha(2A)-adrenergic receptor knockout mice suggested that the alpha(2A)-receptor
subtype inhibits neurotransmitter release with higher speed and at
higher action potential frequencies than the alpha(2C)-adrenergic
receptor. Here we investigated whether these functional differences
between presynaptic alpha(2)-adrenergic receptor subtypes are the
result of distinct signal transduction kinetics of these two receptors
and their coupling to G proteins. alpha(2A)- and alpha(2C)-receptors
were stably expressed in HEK293 cells at moderate ( approximately
2 pmol/mg) or high (17-24 pmol/mg) levels. Activation of G protein-activated
inwardly rectifying K(+) (GIRK) channels was similar in extent and
kinetics for alpha(2A)- and alpha(2C)-receptors at both expression
levels. However, the two receptors differed significantly in their
deactivation kinetics after removal of the agonist norepinephrine.
alpha(2C)-Receptor-activated GIRK currents returned much more slowly
to base line than did alpha(2A)-stimulated currents. This observation
correlated with a higher affinity of norepinephrine at the murine
alpha(2C)- than at the alpha(2A)-receptor subtype and may explain
why alpha(2C)-adrenergic receptors are especially suited to control
sympathetic neurotransmission at low action potential frequencies
in contrast to the alpha(2A)-receptor subtype.
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