Autoreceptors alpha

Boehm, S. and Huck, S. Inhibition of N-type calcium channels the only mechanism by which presynaptic alpha 2-autoreceptors control sympathetic transmitter release. Eur J. Neurosci. 8 1924-1931,1996. 

Clonidine (Catapres). Clonidine is largely used to treat high blood pressure. Although we don t fully understand how clonidine acts, it appears to reduce norepinephrine activity by stimulating a norepinephrine receptor known as the alpha-2 receptor. When clonidine binds to alpha-2 receptors on norepinephrine neurons, so-called autoreceptors, the cells are tricked into believing that there is already sufficient norepinephrine released and thus decrease any additional release of norepinephrine. As one might anticipate, clonidine is somewhat effective at reducing the hyperactivity and impulsivity of ADHD. It does not, however, provide nearly as much benefit for the inattention of ADHD. 

A recent positron emission tomography (PET) study in which the radiolabeled serotonin precursor alpha C methyl tryptophan was used provides empirical evidence of decreased 5-HT synthesis in frontal and thalamic regions and increased 5-HT synthesis in contralateral cerebellar dentate regions (Chugani et al., 1997). These findings are consistent with findings of increased 5-HTm inhibitory autoreceptor sensitivity in adult autistic patients (Hollander et al., 2000 Novotny et al., 2000), since these receptors are prevalent in frontal and thalamic, but not cerebellar, regions. 

On the other hand, alpha 2 receptors are the only presynaptic noradrenergic receptors on noradrenergic neurons. They regulate NE release and so are called autoreceptors. Presynaptic alpha 2 autoreceptors are located both on the axon terminal,... 

FIGURE 5—20. Both types of presynaptic alpha 2 autoreceptors are shown here. They are located either on the axon terminal, where they are called terminal alpha 2 receptors, or at the cell body (soma) and nearby dendrites, where they are called somatodendritic alpha 2 receptors. 

FIGURE 5—44. This figure shows how norepinephrine can function as a brake for serotonin release. When norepinephrine is released from nearby noradrenergic neurons, it can diffuse to alpha 2 receptors, not only to those on noradrenergic neurons but as shown here, also to these same receptors on serotonin neurons. Like its actions on noradrenergic neurons, norepinephrine occupancy of alpha 2 receptors on serotonin neurons will turn off serotonin release. Thus, serotonin release can be inhibited not only by serotonin but, as shown here, also by norepinephrine. Alpha 2 receptors on a norepinephrine neuron are called autoreceptors, but alpha 2 receptors on serotonin neurons are called heteroreceptors. 

FIGURE 8—13. If an alpha 2 agonist such as clonidine, is administered, it will have much the same action as norepinephrine (NE) itself both at somatodendritic alpha 2 autoreceptors and at terminal alpha 2 autoreceptors. This action is that of reducing both neuronal impulse in NE neurons and release of NE from noradrenergic axon terminals. Thus, alpha 2 agonists will decrease the symptoms associated with anxiety, especially the autonomic symptoms of dilated pupils, tachycardia, tremor, and sweating. 

Norepinephrine One theory about the biological basis of panic disorder is that there is an initial excess of norepinephrine (Fig. 9—3). This theory is supported by evidence that panic disorder patients are hypersensitive to alpha-2 antagonists and hyposensitive to alpha-2 agonists. Thus, yohimbine, an alpha-2 antagonist, acts as a promoter of norepinephrine release by cutting the brake cable of the presyn-aptic norepinephrine autoreceptor, as shown earlier in Figure 7—6. The consequence... 

Trendelenburg AU, Philipp M, Meyer A, et al. All three alpha-2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons. Naunyn Schmiedebergs Arch Pharmacol. 2003 368 504-512. 

Figure 4.4 Remeron blocks alpha-2 receptors on neurons that make serotonin and norepinephrine (noradrenaline). Alpha-2 autoreceptors are found on neurons that make norepinephrine. When norepinephrine is released in the synapse, some of it binds to autoreceptors, which tells the neuron to stop releasing neurotransmitters. Alpha-2 heteroreceptors are receptors found on neurons that do not make norepinephrine. Heteroreceptors also provide negative feedback to the neuron releasing a neurotransmitter (serotonin in this diagram).

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