Parasympathetic
The part of the autonomic nervous system that originates in the cranial nerves (and traditionally, the sacral part of the spinal cord); the craniosacral autonomic system.
Sympathetic
the part of the autonomic nervous system that originates in the thoracic and lumbar parts of the spinal cord; the thoracolumbar autonomic system.
Enteric nervous system (ENS)
The enteric nervous system (ENS) is a semiautonomous part of the ANS located in the gastrointestinal (GI) tract, with specific functions for the control of this organ system.
Adrenergic, noradrenergic
A nerve ending that releases norepinephrine as the primary transmitter; also, a synapse in which norepinephrine is the primary transmitter.
Adrenoceptor, adrenergic receptor
A receptor that binds, and is activated by, one of the catecholamine transmitters or hormones (norepinephrine, epinephrine, dopamine) and related drugs.
Adrenergic Transmission
Norepinephrine (NE) is the primary transmitter at the sympathetic postganglionic neuron-effector cell synapses in most tissues. Important exceptions include sympathetic fibers to thermoregulatory (eccrine) sweat glands and probably vasodilator sympathetic fibers in skeletal muscle, which release acetylcholine. Dopamine may be a vasodilator transmitter in renal blood vessels, but norepinephrine is a vasoconstrictor of these vessels.
Synthesis and storage
The synthesis of dopamine and norepinephrine requires several steps. After transport across the cell membrane, tyrosine is hydroxylated by tyrosine hydroxylase (the rate-limiting step) to DOPA (dihydroxyphenylal-anine), decarboxylated to dopamine, and (inside the vesicle) hydroxylated to norepinephrine. Tyrosine hydroxylase can be inhibited by metyrosine. Norepinephrine and dopamine are transported into vesicles by the vesicular monoamine transporter (VMAT) and are stored there. Monoamine oxidase (MAO) is present on mitochondria in the adrenergic nerve ending and inactivates a portion of the dopamine and norepinephrine in the cytoplasm. Therefore, MAO inhibitors may increase the stores of these transmitters and other amines in the nerve endings. VMAT can be inhibited by reserpine, resulting in depletion of transmitter stores.
Release and termination of action
Dopamine and norepinephrine are released from their nerve endings by the same calcium-dependent mechanism responsible for acetylcholine release (see prior discussion). In contrast to cholinergic neurons, noradrenergic and dopaminergic neurons lack receptors for botulinum and do not transport this toxin into the nerve terminal. Termination of action is also quite different from the cholinergic system. Metabolism is not responsible for termination of action of the synaptic catecholamines, norepinephrine and dopamine. Rather, diffusion and reuptake (especially uptake-1, by the norepinephrine transporter, NET, or the dopamine transporter, DAT) reduce their concentration in the synaptic cleft and stop their action. Outside the cleft, these transmitters can be metabolized—by MAO and catechol-O-methyltransferase (COMT)—and the products of these enzymatic reactions are excreted. Determination of the 24-h excretion of metanephrine, normetanephrine, 3-methoxy-4-hydroxymandelic acid (VMA), and other metabolites provides a measure of the total body production of catecholamines, a determination useful in diagnosing conditions such as pheochromocytoma. Inhibition of MAO increases stores of catecholamines in nerve endings and has both therapeutic and toxic potential. Inhibition of COMT in the brain is useful in Parkinson’s disease.
Drug effects on adrenergic transmission
Drugs that block norepinephrine synthesis (eg, metyrosine) or catecholamine storage (eg, reserpine) or release (eg, guanethidine) were used in treatment of several diseases (eg, hypertension) because they block sympathetic but not parasympathetic functions. Other drugs promote catecholamine release (eg, the amphetamines) and predictably cause sympathomimetic effects.
1. Alpha receptors—These are located on vascular smooth muscle, presynaptic nerve terminals, blood platelets, fat cells (lipocytes or adipocytes), and neurons in the brain. Alpha receptors are further divided into 2 major types, α1 and α2. These 2 subtypes constitute different families and use different G-coupling proteins.
2. Beta receptors—These receptors are located on most types of smooth muscle, cardiac muscle, some presynaptic nerve terminals, and lipocytes. Beta receptors are divided into 3 major subtypes, β1, β2, and β3. These subtypes are rather similar and use the same Gs-coupling protein.
Cholinergic
A nerve ending that releases acetylcholine; also, a synapse in which the primary transmitter is acetylcholine.
Cholinoceptor, cholinergic receptor
A receptor that binds, and is activated by, acetylcholine and related drugs.
Cholinergic Transmission
Acetylcholine (ACh) is the primary transmitter in all autonomic ganglia and at the synapses between parasympathetic postganglionic neurons and their effector cells. It is the transmitter at postganglionic sympathetic neurons to the thermoregulatory sweat glands. It is also the primary transmitter at the somatic (voluntary) skeletal muscle neuromuscular junction.
Synthesis and storage
Acetylcholine is synthesized in the nerve terminal by the enzyme choline acetyltransferase (ChAT) from acetyl-CoA (produced in mitochondria) and choline (transported across the cell membrane).
Release of acetylcholine
Release of transmitter stores from vesicles in the nerve ending requires the entry of calcium through calcium channels and triggering of an interaction between SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) proteins. The several types of botulinum toxins are able to enter cholinergic nerve terminals and enzymatically alter synaptobrevin or one of the other docking or fusion proteins to prevent the release process.
Termination of action of acetylcholine
The action of acetylcholine in the synapse is normally terminated by metabolism to acetate and choline by the enzyme acetylcholinesterase in the synaptic cleft.
Drug effects on synthesis, storage, release, and termination of action of acetylcholine
Drugs that block the synthesis of acetylcholine (eg, hemicholinium), its storage (eg, vesamicol), or its release (eg, botulinum toxin) are not very useful for systemic therapy because their effects are not sufficiently selective (ie, PANS and SANS ganglia and somatic neuromuscular junctions all may be blocked). However, because botulinum toxin is a very large molecule and diffuses very slowly, it can be used by injection for relatively selective local effects.
Muscarinic receptors
As their name suggests, these receptors respond to muscarine (an alkaloid) as well as to acetylcholine. The effects of activation of these receptors resemble those of postganglionic cholinergic nerve stimulation. Muscarinic receptors are located primarily on autonomic effector cells (including heart, vascular endothelium, smooth muscle, presynaptic nerve terminals, and exocrine glands). Evidence (including their genes) has been found for 5 subtypes, of which 3 appear to be important in peripheral autonomic transmission. All 5 are G-protein-coupled receptors.
Dopaminergic
A nerve ending that releases dopamine as the primary transmitter; also a synapse in which dopamine is the primary transmitter.
Figure 1. Parasympathetic and sympathetic divisions of the autonomic nervous system with the somatic motor system
Figure 2. Most important cholinoceptors
Figure 3. Adrenoceptors
Figure 4. Direct effects of autonomic nerve activity on some organ systems
Figure 5. G-protein–linked second messengers
Join Art of Medics
Become Part of Art of Medics for further scientific purposes