The Autonomic Nervous System Flashcards
Regulates the function of smooth muscle and cardiac muscle and also controls some aspects of metabolism
-involuntary
Autonomic Nervous System (ANS)
The ANS is centrally regulated by nuclei in the
Medulla, Pons, Hypothalamus, and Spinal cord
Some examples of tissues that are modulated by the ANS include
Cardiovascular, renal, GI, and Endocrine
Afferent tracts that affect the ANS are classified as
- ) Visceral afferents
- ) Somatic Afferents
- ) Central chemo afferents
- ) Cognitive components of CNS
Information regarding anger, arousal, stress, etc
Cognitive components of the CNS
Designed for coping with acute challenges such as elevations in heart rate and blood pressure
Sympathetic nervous system (SNS)
Very active during resting conditions and chronically regulates metabolism and cardiovascular function
Parasympathetic nervous system (PSNS)
Upregulated to help counteract elevated SNS activity
-more localized in its action than the SNS
PSNS
The sympathetic chain is a series of ganglia located on either side of the vertebral column. What type of neurons are preganglionic SNS neurons?
Cholinergic fibers (i.e. ACh is their primary neurotransmitter)
Dendrites and cell bodies of the post-ganglionic SNS fibers express ACh receptors, and these post-ganglionic cholinergic nreceptors can also bind
Nicotine
Dendrites and Cell bodies of Post ganglionic SNS fibers have receptors that are thus identified as
Cholinergic-nicotinic (N2) receptors
When choinergic-nicotinic receptors are bound to ACh or nicotine, they are activated and allow
Inward Na+ or Ca2+ current
Branching of the axons of pre- and post-ganglionic fibers explains, in part, the diffuse action of the
SNS
Post-ganglionic SNS fibers are considered to be
Noradrenergic (use norepinephrine as primary neurotransmitter)
Cell plasma membranes of effector tissues that are innervated by the SNS fibers express
Adrenergic receptors
Adrenergic receptors (adrenoceptors) are grossly classified as type α and β. These receptor families are subclassified as type
α1, α2, β1, β2, and β3
The specific complement of receptor isoforms determines specificity of the response to
Adrenergic stimulation
Adrenoreceptors belong to the family of
G-protein coupled receptors
Can mobilize phospholipase C, and in turn ligand-gated Ca2+ channels can be activated
α1 adrenoreceptors
Binding of adrenergics to α1 receptors in smooth muscle results in what 5 things?
- ) activation of Gi proteins
- ) Decrease in cGMP and cAMP production
- ) Opening of membrane Ca2+ channels
- ) Increase in sarcoplasmic [Ca2+]
- ) Vasoconstriction
Often associated with inhibitory effects on GI smooth
muscle contractility, inhibition of some glandular secretions, and inhibition of neurotransmitter
secretion
Activation of α2 adrenoreceptors
Located on the prejunctional membrane of some post-ganglionic SNS fibers (e.g., cardiovascular)
α2 receptors
When activated by adrenergics, these α2 receptors are involved in
Down regulating neurotransmitter release (negative feedback)
Closely associated with stimulating Gs protein/cAMP signaling
β1 and β2 adrenoreceptors
Predominant in the heart
β1 receptors
Also expressed within the heart and couple to both stimulatory (Gs) and inhibitory (Gi) signaling motifs
-also found in many smooth muscle beds
β2 receptors
In the heart, the activation of β1 and β2 receptors results in increased
Heart rate (chronotropy) and cardiac contractility (inotropy)
Also couple to Gi protein-mediated pathways which induce negative inotropy
Cardiac β2 receptors
Associated with the relaxation of smooth muscle, hepatic glycogen metabolism, and glycogenolysis in skeletal muscle
β2 receptors
In the kidney, activation of β1 receptors stimulates
Renin secretion from JG cells
Synthesized in the axon termini of SNS post ganglionic neurons
Norepinephrine
What are the steps of norepinephrine synthesis?
Tyrosine —> L-dopa —>Dopamine —> Norepinephrine
Dopamine is converted to norepinephrine by
Dopamine β-hydroxylase
Norepinephrine can be converted to epinephrine by
Phenolethaolamine N-methyltransferase
A catcholamine that acts through two receptor isoforms
Dopamine
Expressed within the vascular smooth muscle beds of the cerebral, renal, coronary and mesenteric circulations
Type 1 dopamine receptor (DA1)
DA1 induces
Vasodilation
Expressed within presynaptic SNS fibers and SNS ganglia
Type 2 dopamine receptor (DA2)
Inhibits the secretion of norepinephrine as well as SNS ganglionic transmission
DA2
After diffusing across the synapse, adrenergics bind to adrenoceptors on the
Post-synaptic membrane of the effector tissue
Adrenergics can be degraded by
Catechol-O-methyl transferase (COMT) and/or monoamine oxidase (MAO)
Secrets epinephrine and to a much lesser degree, norepinephrine
The adrenal medulla
Preganglionic SNS fibers terminate within the adrenal medulla and synapse with modified post-ganglionic SNS neural cells called
Chromaffin cells
Chromaffin cells synthesize
Epinephrine and norepinephrine
Chromaffin cells are stimulated by
ACh
Adrenal-derived epi supports the action of the norepi that is locally secreted from
Post-ganglionic SNS fibers
Has a high binding affinity for both α and β adrenoreceptors
-dose-dependent
Epinephrine
At all doses, Epinephrine is a potent
β1 agonist
At a low dose, epinephrine tends to bind B2 receptors and induce
Vasodilation
At a high dose, epinephrine binds α1 adrenoreceptors and thus induces
Vasoconstriction
A potent α1 and β1 agonist and thus augments both systolic (β1) and diastolic (α1) blood pressure
Norepinephrine
At lower doses, norepinephrine does not have as much of an effect on cardiac function, but instead exerts more of a
Presser effect (α1 mediated vasoconstriction)
Norepinephrine has a lower affinity for
β2 adrenoreceptors
So called beta blockers (e.g., atenolol and metoprolol) are type β1 adrenoceptor antagonists; these agents are used to
Lower heart rate and contractility
Commonly used beta blockers with a high degree of specificity against β1 adrenoceptors
Atenolol and metoprolol
The SNS stimulates increased arterial BP through
Increased cardiac output (B1) and vasoconstriction (a1)
What is responsible for the increased blood flow to contracting skeletal muscle seen in SNS response?
B2
What is responsible for the concurrent decreased blood flow to non-contracting skeletal muscle and the GI tract?
a1
SNS response of increased glycolysis in the liver and skeltal muscle is due to
B2 activation
What mediates the following SNS responses?
- ) Decreased insulin secretion
- ) Upregulated glycogenolysis resulting in increased plasma glucose level
- ) a2 and pancreatic B cells
2. ) B2 activation, hepatocytes, and skeletal muscle
What mediates the following SNS responses?
- ) Bronchial smooth muscle relaxation
- ) Increased platelet aggregation
- ) B2 ativation
2. ) a2 activation
Compounds which stimulate adrenoceptor activity (adrenoceptor agonists)
Sympathomimetics
Endogenous as well as pharmacologic adrenoreceptor agonists
Epinephrine and norepinephrine
Low concentrations of epinephrine stimulates both B1 and B2 activity whereas high concentrations function as more of an
a1 agonist
A very effective a1 and B1 agonist but has little B2 effect
Norepinephrine
Impair SNS activity by blocking adrenoceptor activity
Adrenoreceptor antagonists
Suppress vascular smooth muscle tone and thus are useful for reducing hypertension
Alpha blockers
Non-specific alpha blockers have a suppressive effect on presynaptic a2 receptors and will cause
Reflex tachycardia
Widely used to control angina and hypertension
Beta blockers
Beta agonists are indicated to control
Asthma
Beta blockers with a relatively high specificity for the B1 adrenoreceptor
Atenolol and Metoprolol
An example of a non-specific beta blocker is
Propranolol
Cell bodies of the preganglionic PSNS neurons originate within the
Brainstem and sacral region of the spinal cord
Myelinated axons emerging from the brainstem are distributerd within which 4 nerves?
Cranial Nerves
- ) III (oculomotor)
- ) VII (facial)
- ) IX (glossopharyngeal)
- ) X (vagus)
Approximately 75% of the axons of preganglionic PSNS fibers are in the
Vagus nerve
Myelinated axons of the sacral PSNS neurons are distributed with
Pelvic nerves
These fibers are choinergic and terminate in ganglia that are seated very near to the effector tissues
Preganglionic PSNS neurons
Like postganglionic SNS fibers, post-ganglionic PSNS fibers have
Cholinergic-nicotinic receptors (and are unmyelinated)
All pre-ganglionic ANS neurons are
Cholinergic
Dendrites and cell bodies of all post-ganglionic ANS neurons express
Cholinergic nicotinic receptors
Cholinergic nicotinic receptors are functionally classified as
Ligand-coupled (or ligand-activated) Na+ channels
Effectors that respond to PSNS activity posses which type of receptors?
-G-protein coupled receptors
Cholinergic-muscarinic (CM) receptors
ACh is synthesized in the PSNS nerve termini via the reaction between
Acetyl-CoA and choline
ACh synthesis is fairly exclusive to
Pre-ganglionic ANS fibers and Post-ganglionic PSNS fibers
Can synthesize ACh, but rely upon extracellular choline as the substrate for ACh production
α motor neurons
Binds to cholinergic receptors (either muscarinic or nicotinic) on the post-synaptic membrane
ACh
Upon binding, ACh is rapidly degrade by
ACh esterase (cholinesterase)
A hydrolytic product of cholinesterase activity, can be re-uptaken by the presynaptic terminus and recycled for the re-synthesis of ACh
Choline
Compounds that can activate PSNS activity
Chiolinomimetics
Compounds which can impair PSNS activity
Muscarine antagonists
Muscarine antagonists will block the effects of (post-ganglionic) muscarine, and thus have a wide variety of uses. A common example is
Atropine
Uses include:
- ) Anesthesia: block vagal activity to reduce salivary and bronchial secretions and alleviate the inhibition of heart rate
- ) Pupil dilation
- ) Prevention of motion sickness
- ) Reduction in intestinal spasm
Muscarine antagonists such as atropine
