Neurotransmitters of the peripheral nervous system
In the synapses of the peripheral nervous system (PNS), two main neurotransmitters play a key role: acetylcholine and norepinephrine.
The effects of these substances strictly depend on the part of the system where they are released and the receptors with which they interact. For instance, in the somatic nervous system, acetylcholine is exclusively an excitatory neurotransmitter. However, in the neuroeffector synapses of the autonomic nervous system (ANS), both acetylcholine and norepinephrine can induce either excitation or inhibition—the final outcome depends entirely on the physiological properties of the postsynaptic receptors.
Localization of acetylcholine release:
- Neuromuscular junctions of the somatic nervous system.
- Ganglionic synapses of the entire autonomic nervous system.
- Neuroeffector synapses of the parasympathetic division.
- Neuroeffector synapses of the sympathetic division, restricted to sweat glands and skeletal muscle blood vessels.
Localization of norepinephrine release:
- The majority of neuroeffector synapses of the sympathetic nervous system.
Neurotransmitters of the central nervous system
In the central nervous system, neurotransmitters perform more complex tasks and are divided into three functional groups:
- Excitatory neurotransmitters. The principal representative is glutamate. It is the primary excitatory agent responsible for transmitting the vast majority (up to 80%) of signals in the central nervous system.
- Regulatory neurotransmitters. Their role is to adjust neuronal excitability, determine the level of arousal, and shape the motivational-emotional background.
- Acetylcholine maintains the baseline tone of neural centers regardless of whether the body is asleep or awake.
- Norepinephrine additionally activates these centers during stress and intense exertion.
- Dopamine is critical for regulating movement and maintaining normal muscle tone.
- Serotonin acts as a safety valve, containing excessive excitation within necessary limits.
- Inhibitory neurotransmitters. These include GABA (gamma-aminobutyric acid) and glycine. They are capable of selectively and temporarily blocking the passage of nerve impulses, adapting to the current functional state of the body.
Cotransmitters and neuromodulators
In addition to the primary transmitter, presynaptic terminals often release supplementary substances—cotransmitters. Their main function is the fine-tuning (modulation) of postsynaptic membrane sensitivity.
- In adrenergic synapses, dopamine, ATP, neuropeptide Y, and related peptides can act as cotransmitters.
- In cholinergic synapses, this role is performed by vasoactive intestinal peptide (VIP).
A distinct category consists of neuromodulators—biologically active compounds that modulate the potency of primary neurotransmitters:
- Histamine increases the susceptibility of nerve centers to basic mediators.
- Substance P is directly involved in the conduction of pain and emotional arousal, variously modulating synaptic transmission.
- Enkephalins and endorphins are a crucial part of the antinociceptive system. They effectively inhibit the release of major mediators during intense pain stimulation.
Receptor classification
Postsynaptic membrane receptors are classified based on their sensitivity to specific chemical substances. All types of receptors are present in the CNS, whereas strict specialization is observed in the periphery.
| Receptor type | Excited by | Main localization (PNS) |
|---|---|---|
| Nicotinic acetylcholine receptors (nicotinic) | Tobacco alkaloid — nicotine (in low doses) | Neuromuscular junctions, autonomic ganglia, sympathetic cholinergic synapses |
| Muscarinic acetylcholine receptors (muscarinic) | Crustacean and fungal toxin — muscarine | Neuroeffector synapses of the parasympathetic nervous system |
| Adrenergic receptors ($\alpha$, $\beta_1$, $\beta_2$) | Norepinephrine | Neuroeffector synapses of the sympathetic nervous system |
Briefly: answers to topical questions
Which enzymes are involved in the synthesis and degradation of acetylcholine?
Two main enzymes are involved in the metabolism of acetylcholine, ensuring its formation and breakdown.
- Choline acetyltransferase (choline acetylase) is an enzyme that catalyzes the biosynthesis of acetylcholine from choline and acetyl-CoA in the cytoplasm of cholinergic nerve terminals.
- Acetylcholinesterase is an enzyme of postsynaptic terminals that performs rapid hydrolysis of the mediator in the synaptic cleft, forming choline and acetic acid.
What subtypes are adrenergic receptors divided into and what physiological effects do they cause?
Adrenergic receptors are divided into alpha and beta subtypes, causing various metabotropic effects.
- $\alpha_1$ and $\beta_1$ cause excitation of the postsynaptic cell.
- $\alpha_2$ and $\beta_2$ cause inhibition.
The response of the effector organ to norepinephrine directly depends on the prevailing receptor type on the postsynaptic membrane (e.g., bronchial relaxation or vasoconstriction).
What types of glutamate receptors exist in the CNS?
Excitatory amino acid receptors for glutamate are subdivided into three main ligand-gated types.
- Kainate receptors — one of the types of glutamate receptors.
- AMPA ($\alpha$-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors — upon activation, open ion channels for sodium, triggering membrane depolarization.
- NMDA (N-methyl-D-aspartate) receptors are ion channels that are blocked by magnesium ions at rest and open only after prior depolarization by AMPA receptors.
By what mechanisms is the neurotransmitter removed from the synaptic cleft?
Neurotransmitter removal and inactivation occur through several mechanisms:
- Reuptake: transport proteins of the presynaptic membrane return the neurotransmitter to the presynaptic terminal; 80% of norepinephrine undergoes reuptake.
- Enzymatic degradation: for example, acetylcholine is broken down by acetylcholinesterase, and norepinephrine by MAO and COMT.
- Diffusion: part of the neurotransmitter is lost due to diffusion from the synaptic cleft.
- Endocytosis: potential internalization of the signaling molecule-receptor complex.
To remember the localization of cholinergic receptors: N receptors respond to nicotine and are located in neuromuscular junctions. M receptors respond to muscarinic agents and provide mild (parasympathetic) regulation of organs.
Class and exam questions
Can a single neuron synthesize multiple different neurotransmitters?
No, according to the classical Dale's principle, each nerve cell synthesizes only one primary neurotransmitter. However, additional substances—cotransmitters—may be released along with it.
What determines whether a neurotransmitter effect is excitatory or inhibitory?
In neuroeffector junctions of the autonomic nervous system, the net effect of the neurotransmitter (acetylcholine or norepinephrine) depends entirely on the properties of the receptors on the postsynaptic membrane. In contrast, in the somatic system, acetylcholine always causes excitation alone.
What is the function of enkephalins and endorphins?
These substances are part of the body's antinociceptive (pain-relieving) system. They inhibit the release of primary transmitters at synapses during painful stimuli, reducing pain intensity.
Where are muscarinic cholinergic receptors located?
They are localized on target organs in neuroeffector junctions of the parasympathetic nervous system and are specifically stimulated by muscarine.
What else to study on this topic
- Mechanism of action of neurotransmitters on the postsynaptic membrane
- Specific properties of $\alpha$- and $\beta$-adrenergic receptors
- The role of dopamine in the regulation of muscle tone and movement
- Principles of the antinociceptive system
- Differences in the functioning of N- and M-cholinergic receptors
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