Neurotransmitters and Receptors of the Autonomic Nervous System

General Chemical Organization of the ANS

Signals in the autonomic nervous system are transmitted chemically. Several types of neural connections exist based on the specific substance utilized. The classic classification includes cholinergic and noradrenergic transmission, alongside serotonergic, dopaminergic, and purinergic mechanisms.

The final response of the target organ is determined by the neurotransmitter-receptor combination. A single tissue may contain multiple receptor subtypes, making the organ's response highly specific.

Based on their localization, receptors are divided into:

• Postsynaptic — located directly on the effector organ cells.
• Presynaptic — located on the nerve terminal itself, functioning via feedback loops to regulate neurotransmitter release.
• Extrasynaptic — located in the extracellular space, responding to biologically active substances circulating in body fluids.

Signal Transmission in Sympathetic and Parasympathetic Divisions

The pathway from the central nervous system to the effector organ in the ANS always consists of a two-neuron chain: preganglionic and postganglionic.

Parasympathetic Division Both neurons in this chain utilize the same neurotransmitter — acetylcholine.

1. In the autonomic ganglion, acetylcholine is released by the first neuron and binds to nicotinic acetylcholine receptors (nAChRs) on the second neuron.
2. At the target organ level, the postganglionic fiber releases acetylcholine again, but here it acts on muscarinic acetylcholine receptors (mAChRs).

Sympathetic Division Neurotransmitter switching occurs along this pathway.

1. Ganglionic transmission is identical to the parasympathetic division: acetylcholine is released, stimulating nAChRs on the second neuron.
2. The terminal of the postganglionic fiber releases norepinephrine. It interacts with specific adrenergic receptors ($\alpha$- and $\beta$-types) on the effector organ.

Classification of Major Receptors

Receptor systems are divided into two major groups based on their sensitivity to specific chemical agents.

Cholinergic Receptors Respond to acetylcholine. They are subdivided into:

• Muscarinic receptors ($M$ receptors) — the primary targets of the parasympathetic system on effector organs.
• Nicotinic receptors ($N$ receptors) — located in sympathetic and parasympathetic ganglia, mediating signal transmission between nerve cells.

Adrenergic Receptors Stimulated by norepinephrine and epinephrine. They include two main classes:

• $\alpha$-adrenergic receptors (subtypes $\alpha_1$ and $\alpha_2$).
• $\beta$-adrenergic receptors (subtypes $\beta_1$ and $\beta_2$).

Physiological Properties of Fibers and Ganglia

Autonomic neural structures differ significantly from somatic ones. Nerve fibers exhibit low excitability, prolonged absolute refractoriness, and low lability (no more than 15 impulses/sec). Conduction velocity is extremely low: in preganglionic fibers (B fibers), it is 3–20 m/s, dropping to 0.5–3 m/s in postganglionic fibers (C fibers). The action potential duration is prolonged up to 150 ms due to prominent after-potentials.

Autonomic ganglia act as complex integrative centers with low baseline activity. They exhibit spatial and temporal summation, as well as network phenomena such as divergence (multiplication), convergence, and occlusion. Synaptic delay ranges from 1 to 25 ms. A characteristic feature of ganglia is their high sensitivity to blood-borne epinephrine, which acts as a modulator of synaptic transmission.