Receptor Regulation

Neurotransmitter receptors are proteins which are synthesised within the cell bodies of nerve cells. The information to make different receptors is coded for in DNA, the protein receptors are made in rough endoplasmic reticulum and transported to the cell membrane for implantation.

Receptors have a fixed life-span, after which they are re-absorbed into the cell and their constituent amino acids recycled. The manufacture and degradation of receptors is closely regulated by the cell and an appropriate balance achieved.

Receptor up and down-regulation

The nerve cell frequently has an internal 'set point', setting upper and lower thresholds for desired stimulation by a neurotransmitter. When neurotransmitters increase or decrease beyond the threshold for that neurone, it will often respond by reducing or increasing the number of receptors.

Down- regulation

Prolonged exposure to a neurotransmitter agonist, or raised levels of neurotransmitter due to neuronal dysfunction will lead to a compensatory decrease in the number of receptors over a period of time. This mechanism also explains why drugs which are agonists often lose their effects over time.
For example, a heroin user will inevitably have levels of heroin in their brain which consistently occupy opioid receptors. Over a period of time the post synaptic neurone will not respond to usual amounts of heroin, increased amounts will be required to have the desired effect.

Antidepressants and down regulation

Although antidepressants raise the brain's level of neurotransmitters within hours, they do not affect a patient's mood for several weeks often some time between two to six weeks.

This suggests that antidepressants work by altering the number and sensitivity of post-synaptic receptors to the neurotransmitter rather than just raising neurotransmitter levels. The neurotransmitters implicated in depression are the monamines, serotonin and noradrenaline.

Those with depression, it is speculated, possess post-synaptic receptors that have grown hypersensitive and they have most likely become this way due to a depletion in the level of monoamines. Antidepressants work by raising the level of neurotransmitters in the synaptic cleft, but this by itself does not alter the course of depression. Instead, this increased level of neurotransmitters acts over several weeks to desensitize or 'down-regulate' the post-synaptic receptors. Once these receptors become desensitized, the individual's depression lifts.

Up- regulation

When there is a prolonged lack of stimulation due to reduced amounts of neurotransmitter, there is often an increase in the number of cell receptors and hence the post-synaptic neurone is hypersensitive.

The time course of up and down regulation takes place over a period of weeks rather than hours and not all receptors show this effect.

Autoreceptors

Autoreceptors play a role in balancing the amount of neurotransmitter secreted. These receptors are usually inhibitory, reducing both the synthesis and secretion of neurotransmitter, they are found on the presynaptic membrane.