What Are Neurotransmitters and How Do They Function in the Autonomic Nervous System?

By Chandan Sekhon - Medicine Student @ Peterhouse, Cambridge

 

The autonomic nervous system (ANS) can be subdivided into two main pathways – the sympathetic and parasympathetic nervous systems. In order for the body to make use of these systems, it uses neurotransmitters to control and mediate involuntary actions allowing the body to respond to stimuli.


General Overview of the PNS and SNS:

The sympathetic nervous system (SNS) is primarily involved in stimulating the body’s fight or flight response by directing rapid involuntary responses to harmful or stressful stimuli. In contrast, the parasympathetic nervous system (PNS) is involved in mediating the body’s rest and digest response, where energy is conserved for later use. Predominantly, acetylcholine (Ach) is used in the PNS and a group of neurotransmitters called catecholamines are most commonly used in the SNS. This group of neurotransmitters includes adrenaline, noradrenaline (NA) and dopamine.


Synthesis of neurotransmitters:

Ach has uses in both the PNS and SNS, and in the ANS. For Ach to be synthesised, the molecule choline is required. This can be obtained from the diet (as very little is produced in neurones), or it can be recycled from Ach breakdown. The choline is acetylated by an enzyme (ChAT) with the acetyl group being derived from acetyl CoA during the link reaction of respiration. The recycling of choline is crucial for Ach abundance.


Catecholamine synthesis begins with the amino acid tyrosine (obtained from the diet usually). From here, tyrosine hydroxylase (TH) converts L-tyrosine into L-DOPA. which is the rate-limiting step in catecholamine biosynthesis. Often immediately afterwards, this is metabolised into dopamine by DOPA-decarboxylase. This is the first main step in the production of adrenaline and NA, as well as dopamine. In cells where NA is used, dopamine can then be converted into NA by being hydroxylated. This conversion takes place in dopamine storage vesicles. In the adrenal medulla, NA can be converted into adrenaline. This synthesis occurs in chromaffin cells, with some synthesis in some neurones in the medulla oblongata


Action:

Following release, Ach acts upon cholinergic receptors at the post-synaptic terminals. These can be classified into two main types – muscarinic (mAchRs) and nicotinic (nAchRs). Depending on the synapse, these receptors will vary in abundance and function. mAchRs are all coupled to proteins inside cells. nAchRs are ion channels which are present at neuromuscular junctions. Most nAchRs are permeable to cations such as Na+ and K+, and their opening causes depolarisation of the membrane. This may stimulate an action potential if the resulting depolarisation exceeds the threshold for that membrane. These two types of receptors perform different roles within the ANS, with nAchRs having short and brief responses, being purely excitatory and solely postsynaptic, and mAchRs having slow and prolonged effects, mediating both inhibition and excitation in target cells and being both pre- and postsynaptic. Depending on the location of the receptors, Ach can have many effects in tissues. For example, M2 muscarinic receptors located in the heart act to slow the heart rate down following stimulation by Ach, while M3 receptors located in the GI tract may help in dilating sphincters upon Ach stimulation.


NA and adrenaline both stimulate similar receptors, but they often do so with varying affinities. NA has a greater affinity for α1-adrenoreceptors than does adrenaline and is involved in actions such as glycogenolysis. α2-adrenoreceptors are involved in platelet clotting and vasoconstriction. These are stimulated by both NA (with higher affinity) and adrenaline (with lower affinity). A key difference between these two neurotransmitters is that adrenaline can bind to both β1 and β2-adrenoreceptors with high affinity, while NA can only bind to β1 receptors, with lower affinity. The β1 receptor is often involved in increasing heart rate and force of contraction of cardiac tissue. β2 receptors can only bind adrenaline and is involved in relaxation of smooth tissue in the respiratory tree and blood vessels supplying the heart and skeletal muscle.


Further reading:

  1. This article gives a general overview of adrenaline and noradrenaline with its key differences and actions: https://www.medicalnewstoday.com/articles/325485

  2. This article gives a very detailed breakdown of how acetylcholine works and what it does. This is very detailed but is an interesting read: https://www.ncbi.nlm.nih.gov/books/NBK557825/

  3. This article describes dopamine (not discussed here) which is another neurotransmitter: https://academic.oup.com/endo/article/151/12/5570/2456083

  4. This article compares dopamine and noradrenaline. Quite detailed but a good read nonetheless: https://www.frontiersin.org/articles/10.3389/fnmol.2019.00334/full