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28 Cards in this Set
- Front
- Back
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Schematic of the ANS:
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2 parts: sympathetic and cholinergic
Cholinergic:Cranial/Sacral (muscarinic receptors) Sympathetic: thoracolumbar (nicotinic receptors) |
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Discuss the ANS in general:
what does it include? what does it not include? |
*‘Visceral’ or ‘Involuntary’ Nervous System
-Heart, blood vessels, smooth muscle, glands, other visceral organs -Does not include skeletal muscle (somatic nervous system) |
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Discuss the 2 divisions of the ANS:
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*Sympathetic = Thoracolumbar Outflow
Required for ‘fight or flight’ responses at times of stress “mobilize body for activity” *Parasympathetic = Craniosacral Outflow Essential for life: conservation of energy, maintenance of organ function with minimal activity “rest and digest” Baseline: mostly PS, some S |
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Components of the Sympathetic NS:
Neurotransmitter of preganglionics-- What kind of receptors-- Result of stimulation of postganglionics-- Effects of neurotransmitter-- |
Preganglionic neurons (with ACh), ganglia, nicotinic receptor, postganglionic neuron--> NE synthesis (or Epi in adrenal medulla).
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Adrenergic Transmission:
Synthesis-- Storage-- Exocytosis-- |
*Synthesis in postganglionic neuron.
-Norepinephrine is synthesized from its precursor, dopamine. -Free norepinephrine is metabolized by monoamine oxidase (MAO) *Storage in vesicles -RESERPINE (old school BP med) blocks the uptake of NE into vesicles *Release through exocytosis -GUANETHIDINE and BRETYLIUM (also old school) block the release of NE into the synaptic cleft |
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Adrenergic Transmission:
Binding to receptors-- Termination of effect-- Co-transmitters-- |
*Binding to receptors (postsynaptic)
*Termination of Effect: -Removal from synaptic cleft NET reuptake is primary means of removal. This can be blocked by inhibitors such as cocaine. Diffusion away from site of receptor with metabolism -Feedback Stimulation of pre-synaptic alpha-2 receptors block further release of NE *Co-transmitters |
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The Mechanism by Which Cocaine Alters Sympathetic Tone:
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Blocks reuptake of NE.
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Normal NE transport:
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*80% of NE goes through NE transporter and is collected in synaptic vesicle.
*20% diffuses away and is degraded by MAO and COMT. |
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Genetic Alterations in Sympathetic receptors:
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It's possible to have some receptors that are more active than normal.
The two polymorphisms shown are associated with increased mortality from heart failure. |
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Mechanisms of Sympathetic Signal Transduction:
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*All autonomic receptors are coupled to GTP-binding proteins with second messenger system (relatively slow).
-Alpha-1 (subtypes 1A, 1B, 1D): Activate phospholipase C; Increase IP3 and Intracellular Ca++ -Alpha-2 (subtypes 2A, 2B, 2C): Inhibition adenylyl cyclase and decrease cAMP -Beta-1/Beta-2: Stimulate adenylyl cyclase and increase cAMP *Different receptors--> different effects. |
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Mechanisms of Sympathetic Signal Transduction diagram:
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The point: it's a multistep process, and different receptors have different effects.
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Relative Receptor Potencies of Norepinephrine and Epinephrine:
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Alpha-1: EPI ≥ NE
Alpha-2: EPI ≥ NE Beta-1: EPI = NE Beta-2: EPI >> NE Beta-3: NE > EPI *ß2 receptors are the big difference! Epi is much more potent; enables NE to be used as a therapy...more to come. |
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Effects of Stimulation of Beta-1 Adrenoreceptors:
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*Heart * (think heart!)
-SA Node: Increased heart rate -AV Node: Increased conduction velocity -HIS-purkinje cells: Increased conduction velocity and automaticity -Cardiac Muscle: Increased contractility *Kidney juxtaglomerular cells-- Increased renin secretion *Some beta-2 and beta-3 effects in the heart. Biggest effect is from ß1. |
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Effects of Stimulation of Beta-2 Adrenoreceptors :
Effects of Stimulation of Beta-3 Adrenoreceptors : |
*Smooth Muscle (think relaxation!)
Arteriolar: Relaxation Bronchiolar: Relaxation Intestinal: Relaxation (reduced motility) Genitourinary: Relaxation (reduced urgency) *Other Muscle Ciliary muscle (eye): relaxation Skeletal muscle: increased potassium uptake *Liver-- Increased glycogenolysis *Pancreatic Islets (Beta Cells)-- Increased insulin secretion *Stimulation of Beta-3 Adrenoreceptors: Lipolysis and Smooth Muscle Relaxation |
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Effects of Stimulation of Alpha-1 Adrenoreceptors :
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Smooth Muscle
Arteriolar*: Contraction Veins*: Contraction Genitourinary: Contraction Intestinal: Relaxation Eye Radial muscle: Contraction Lacrimal glands: Secretion Liver-- Increased glycogenolysis Kidney juxtaglomerular cells-- Decreased renin secretion *Some alpha-2 effects as well here, but mostly alpha-1 |
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Effects of Stimulation of Alpha-2 Adrenoreceptors :
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*Pancreatic Islets (Beta Cells)
Decreased insulin secretion *Presynaptic Receptors Decreased release of norepinephrine |
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Which of the following does NOT result from stimulation of Beta-1 and/or Beta-2 receptors by epinephrine?
Bronchodilation Increased heart rate Increased glycogenolysis Arteriolar vasoconstriction Intestinal muscle relaxation |
Bronchodilation (ß2)
Increased heart rate (ß1) Increased glycogenolysis (ß2) Arteriolar vasoconstriction (alpha!) Intestinal muscle relaxation (ß2) |
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A 30 year old patient is diagnosed with a pheochromocytoma generated by a benign tumor in her right adrenal gland causing excessive release of epinephrine and norepinephrine.
*What signs and symptoms would you expect in this patient? *If you were asked to design a drug to treat the signs and symptoms of pheochromocytoma, what would be its mechanism(s) of action? |
*High blood pressure (from alpha effects), high heart rate. Alpha effects trump beta effects.
*Treatment: alpha blockade followed by beta blockade. |
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Components of the PNS:
Neurotransmitter of preganglionics-- What kind of receptors-- Result of stimulation of postganglionics-- Effects of neurotransmitter-- |
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Cholinergic Transmission I:
Synthesis-- Storage-- Release-- |
Synthesis:
*Choline uptake (which is reduced by hemicholinium); combines with acetyl CoA in presence of choline acetyltransferase (CHAT) produces acetylcholine *Storage in vesicles (Uptake reduced by vesamicol) *Release through exocytosis (Blocked by botulinum toxin) |
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Cholinergic transmission:
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Cholinergic Transmission II:
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*Binding to receptors (postsynaptic)
*Removal from synaptic cleft: Acetylcholinesterase (AChE) is primary means of removal of ACh in synaptic cleft. Choline + Acetate are taken back up into presynaptic neuron. Reuptake of ACh is relatively SMALL. *Feedback? |
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Muscarinic Receptors (M1-M5) and Mechanisms of Signal Transduction I:
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*G-protein coupled receptors: 2nd messenger system with slower response than nicotinic receptors
-M1, M3, M5: all increase release of intracellular calcium and protein phosphorylation; M2, M4: both increase potassium permeabilty and decrease cAMP *M2 -Location: Heart: SA node, Atria, AV node, Ventricles -Result of Stimulation: Increased potassium permeability (inhibitory); Decreased adenylyl cyclase activity (decreased cAMP); Decreased calcium permeability: Slows conduction *There are no specific (M1, M2...) drugs for these! Just anti-muscarinics. |
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Muscarinic Receptors (M1-M5) and Mechanisms of Signal Transduction II:
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M3
Location/Result of Stimulation: Smooth muscle contraction; Relaxation of sphincters; Dilation of vessels through production of NO by vascular endothelium; Increased secretion of glands M1, M4, M5 *There are no specific (M1, M2...) drugs for these! Just anti-muscarinics. |
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Stimulation of Muscarinic Receptors I:
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*Heart
SA Node: Decreased heart rate AV Node: Decreased conduction velocity Muscle: Decreased contractility (vagus is responsible for all of these effects) *Vascular Smooth Muscle Endothelium intact: Relaxation Endothelium removed: Contraction |
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Stimulation of Muscarinic Receptors II:
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*Other Smooth Muscle
Gastrointestinal: Contraction Bronchiolar: Contraction *Eye Sphincter muscle: Contraction Ciliary muscle: Contraction *Glands Increased secretion Salivary; Lacrimal; Nasopharyngeal; Bronchiolar; GI; Pancreatic digestive glands; Skin sweat glands *Sphincters Urinary: Relaxation Gastrointestinal: Relaxation |
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Discuss the Baroreceptor Reflex Arc:
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Stand up --> bp falls --> leads to vasoconstriction (alpha), cardiac stimulation (ß1), and inhibition of cardiac inhibitor.
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Which of the following statements is correct regarding the parasympathetic nervous system?
A. Acetylcholine is synthesized in the postganglionic neuron and is released passively into the synaptic cleft. B. Activation of presynaptic M4 receptors increases release of acetylcholine into the synaptic cleft. C. Removal of acetylcholine from the synaptic cleft is primarily through reuptake and the process is inhibited by cocaine. D. Stimulation of M2 receptors in the heart result in decreased calcium permeability and slowing of heart rate and AV nodal conduction. |
D. Stimulation of M2 receptors in the heart result in decreased calcium permeability and slowing of heart rate and AV nodal conduction.
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