CNSforum The Lundbeck Institute

Anxiety: Noradrenergic receptor systems

Mechanism of action of noradrenaline re-uptake transporters

The action of noradrenaline at the synapse is terminated by its re-uptake across the pre-synaptic membrane. This is an energy dependent process. Sodium/potassium ATPases use energy from ATP hydrolysis to create a concentration gradient of ions across the pre-synaptic membrane that drives the opening of the transporter and co-transport of sodium and chloride ions and noradrenaline from the synaptic cleft. Potassium ions binding to the transporter enable it to return to the outward position. Release of the potassium ions into the synaptic cleft equilibrates the ionic gradient across the pre-synaptic membrane. The noradrenaline re-uptake transporter is then available to bind another noradrenaline molecule for re-uptake.

Noradrenaline a2 adrenergic receptor

There are two different types of adrenoreceptor – the α and β receptors. The α receptors are further classified into α1 and α2 subtypes and the β receptors are further classified into β1, β2 and β3 subtypes. The α2 adrenoreceptors are widely distributed throughout the body and are found in adrenergic neurones, blood vessels, the pancreas and in smooth muscle. Coupled to inhibitory G-proteins,α2 adrenoreceptors have an inhibitory effect on neurotransmission when bound by an agonist.

Mechanism of action of an a2 adrenergic receptor antagonist

An α2 adrenergic receptor antagonist prevents the activation of the α2 adrenergic receptor. The α2 receptor is coupled to inhibitory G-proteins, which dissociate from the receptor following agonist binding, and inhibit both secondary messenger signaling mechanisms and cell depolarisation. Antagonist binding to the α2 adrenergic receptor prevents secondary messenger inhibition and allows cell depolarisation to occur.