Autonomic Nervous System (ANS)

• The autonomic nervous system regulates activities not under direct conscious control, like cardiac muscle, GIT, and exocrine glands.

Divisions of the Nervous System

• The peripheral nervous system and central nervous system are the two main divisions of the nervous system

Peripheral Nervous System Subdivisions

• The peripheral nervous system divides into the efferent division and afferent division.
• These divisions lead to the autonomic system and somatic system.
• The autonomic system is futher subdivided into the enteric, parasympathetic, and sympathetic systems.

Nerve Function

• Afferent (sensory) nerves: conduct signals from organs to the CNS.
• Efferent (motor) nerves: conduct orders from the CNS to organs.

Autonomic Nervous System (ANS) Anatomy

• The ANS is divided anatomically into sympathetic and parasympathetic divisions.
• Sympathetic nerve fibers: originate from the thoracolumbar regions (T1, 4, 5, 11, 12 and L1, 3).
• Parasympathetic nerve fibers: originate from the craniosacral regions of the CNS (cranial nerve nuclei III, VII, IX, X and sacral segments 2, 3, 4).
• The sympathetic nervous system accommodates stressful conditions.
• The parasympathetic nervous system maintains normal conditions.
• Both portions are physiologically antagonistic but increase salivary secretion.
• All organs receive dual supply except the liver and blood vessels.

Autonomic Nerve Fibers

• Autonomic efferent nerve fibers differ from somatic nerves.
• They do not travel directly from the CNS to the effector organ.
• They travel as two nerves separated by a synapse.
• The nerve fiber originating from the CNS is preganglionic, and the next is postganglionic.
• Sympathetic nervous system preganglionic fibers are short, with synapses in paravertebral ganglia.
• Parasympathetic nervous system synapses rely on nearly inside the affected organ followed by a short postsynaptic fiber.
• Somatic motor nerve endings travel directly into skeletal muscles without relying on ganglia.

Neurotransmitter Chemistry

• Autonomic nerves are classified into cholinergic and adrenergic based on transmitter molecules.
• Peripheral autonomic nerve endings that synthesize and release acetylcholine are cholinergic fibers.
• These include all preganglionic nerve endings, somatic motor nerve endings to skeletal muscle, and a few sympathetic postganglionic fibers (supplying sweat glands).
• Most postganglionic sympathetic fibers release norepinephrine and are adrenergic.
• Most autonomic nerves release cotransmitters in addition to the primary transmitter.

Cholinergic Transmission

• Acetylcholine is synthesized in the cytoplasm of nerve endings from acetyl-CoA and choline via choline acetyltransferase (ChAT).
• Acetyl-CoA is synthesized in mitochondria.
• Choline is transported from extracellular fluid into the neuron terminal by a sodium-dependent membrane carrier (carrier A), blocked by Hemicholiniums drugs.
• Acetylcholine (Ach) is transported from the cytoplasm into vesicles by an antiporter carrier (carrier B), which can be blocked by vesamicol.
• Release of Ach occurs when an action potential reaches the terminal and triggers sufficient influx of calcium ions
• Increased Ca2+ destabilizes storage vesicles, interacting with vesicular membrane proteins.
• Fusion of these membranes with the terminal membrane occurs through the interaction of vesicular and synaptosome proteins.

Adrenergic Transmission

• Synthesis of catecholamine transmitters is more complex than that of acetylcholine.
• In most sympathetic postganglionic neurons, norepinephrine is the final product.
• In the adrenal medulla and certain brain areas, norepinephrine is further converted to epinephrine.
• Synthesis terminates with dopamine in dopaminergic neurons of CNS,.
• Synthesis of catecholamine transmitters occurs through several steps, targeted by drugs.
• Tyrosine is converted to dopa, a rate-limiting step in catecholamine transmitter synthesis.
• This can be inhibited by the tyrosine analog metyrosine.
• A high-affinity carrier transports a catecholamines.
• A high-affinity carrier for catecholamines can be inhibited by the reserpine alkaloids, uptake 3, leading to depletion of transmitter stores.
• The carrier transporting norepinephrine into neuronal cells (uptake 1) can be inhibited by cocaine and tricyclic antidepressant drugs.
• This results in increased transmitter activity in the synaptic cleft and tissue receptors.
• Epinephrine from adrenergic nerve endings is Calcium-dependent.
• ATP, dopamine-βhydroxylase, and peptide cotransmitters are also released into the synaptic cleft.
• Indirectly acting sympathomimetics (e.g., tyramine, amphetamines) cause transmitter release from noradrenergic nerve endings after neuronal uptake 1 and not via storage vesicles of neuronal cells (uptake 3).
• Uptake 1 and 3 are called neuronal, while uptake 2 is extraneuronal.
• Norepinephrine and epinephrine can be metabolized by MAO and COMT.
• Monoamine oxidase (MAO) is present in tissues, synaptic clefts, & mitochondria of neuronal cells but not in storage vesicles.

Types of Autonomic Nerve Endings

• Nerve fibers are classified into cholinergic (releasing Ach) and adrenergic (releasing norepinephrine).
• All somatic nerves and all preganglionic nerves (parasympathetic or sympathetic, even those supplying the adrenal medulla) are cholinergic.
• All parasympathetic postganglionic fibers are cholinergic.
• Most sympathetic postganglionic fibers are adrenergic.
• Few sympathetic postganglionic fibers (supplying sweat glands) are cholinergic.

Autonomic Receptor Types

• Key autonomic receptor types include muscarinic, nicotinic, alpha, beta, and dopamine receptors.

Key Autonomic Receptor Actions

Eye

• Iris radial muscle contracts via α1 receptors.
• Iris circular muscle contracts via M3 receptors.
• Ciliary muscle relaxes via β2 receptors and contracts via M3 receptors.
• Ciliary epithelium affects synthesis via β2, α2 receptors.

Heart

• Sinoatrial node accelerates via β1 and decelerates via M2 receptors.
• Ectopic pacemakers accelerate via β1 receptors.
• Contractility increases via β1 and decreases (atria) via M2 receptors.

Blood Vessels

• Skin and splanchnic vessels contract via α1 receptors.
• Skeletal muscle vessels relax via β2 and contract via α1 receptors.
• Endothelium releases EDRF via M3 receptors.

GIT

• Walls relax via α2, β2 and contract via M3 receptors.
• Sphincters contract via α1 and relax via M3 receptors.
• Secretion increases via M3 receptors.

Genitourinary

• Bladder walls relax via β2 and contract via M3 receptors.
• Sphincters contract via α1 and relax via M3 receptors.
• Uterus (pregnant) relaxes via β2 and contracts via M3 receptors.
• Penis and seminal vesicles ejaculate via α1 and erect via M receptors.

Skin

• Pilomotor smooth muscle contracts via α1 receptors.
• Sweat glands have varying effects.
• Thermoregulatory increases via M receptors.
• Apocrine (stress) increases via α receptors.

Metabolic functions

• Liver gluconeogenesis and glycogenolysis increase via β2 receptors.
• Fat cells lipolysis increases via β3 receptors.
• Kidney renin release increases via β1 and decreases via α2 receptors.
• Pancreas (insulin release) has varying effects via β2, α2, and M receptors.
• NN receptors facilitate conduction of nerve action potential (NAP) in autonomic ganglia.
• NM receptors facilitate conduction of NAP in neuromuscular junctions.
• The autonomic nervous system is controlled by the hypothalamus in the CNS.
• The anterior hypothalamus controls the parasympathetic portion.
• The posterior hypothalamus controls the sympathetic portion.