Sympathetic Signaling Flashcards
Where do pre-ganglionic sympathetic neurons originate and terminate?
Pre-ganglionic sympathetic neurons originate in the spinal cord (T1-L2) and release ACh onto nicotinic ACh receptors located in the ganglia of the paravertebral chain
Physiologic effects - vasculature (a1)
Vasoconstriction (increased total peripheral resistance)
Physiologic effects - vasculature (B2)
Vasodilation (decreased total peripheral resistance, increased perfusion)
Physiologic effects - renal vasculature (D1)
Vasodilation
Physiologic effects - cardiac (B1)
Increased heart rate (chronotropoy)
Increased AV conduction velocity
Increased contractility (inotropy)
Postural baroreceptor reflex arc
Activation of the baroreceptor by increased vessel tension due to increased arterial pressure inhibits symmpathetic discharge from the medulla, resulting in vasodilation and decreased heart rate. leading to a decrease in arterial pressure
Relaxation of the baroreceptor due to decreased arterial pressure “disinhibits” sympathetic discharge, resulting in SNS-mediated release of NE at the heart (B1) causing tachycardia and blood vessels (a1) causing vasoconstriction
Physiologic effects - Kidney (B1)
NE acts on B1 receptors in the kidney juxtaglomerular cells, resulting in vasoconstriction and activation of the RAAS system
Physiologic effects - Lungs (B2)
Bronchodilation
Physiologic effects - Eye
Pupil dilation (a1) Increased production of aqueous humor (B2)
Physiologic effect - GI tract
Decreased motility via smooth m. relaxation (B2)
Activation of pre-synaptic A2 receptors on cholinergic neurons inhibits release of ACh, thereby inhibiting ACh-mediated muscle contraction
Physiologic effects - genitourinary
Contraction of ureteral sphincter (a1) - promotes continence
Uterine smooth muscle relaxation (B2)
Physiologic effects - skeletal muscle
Tremor (B2)
Physiologic effects - metabolic
Liver - increased glycogenolysis causing increased blood glucose (B2)
Fat cells: Increased lipolysis (B3)
Pancreas: Decreased insulin secretion (a2)
How is NE synthesized?
Neurons take up tyrosine by active transport and convert it to DOPA by tyrosine hydroxylase; DOPA is converted to dopamine and taken up into storage vesicles where it is converted to NE by dopamine-B hydroxylase
How is NE stored and released?
NE is transported into storage vesicles by active transport by the VMAT pump; within the vesicles NE is protected from degradation by monoamine oxidase (MAO) located on mitochondria
How is NE signaling terminated?
80% of released NE is taken back up into the presynaptic nerve terminal by the NE transporter (NET); most of this NE is taken back into storage vesicles by VMAT and a smaller percentage is metabolized by MAO
Which receptors does NE bind?
A1, A2
B1
Which receptors does adrenal epinephrine bind?
A1, A2
B1, B2
What is the difference between Epi and NE?
Epi binds B2 receptors and NE doesn’t; therefore, Epi causes bronchodilation (i.e. in anaphylaxis) and increased perfusion of muscles
How do A2 heteroreceptors work?
NE binds pre-synaptic A2 receptors on cholinergic neurons, where it inhibits release of ACh; i.e. activation of the SNS indirectly decreases GI motility via this mechanism
Alpha 1 - Receptor Coupling
Gq protein-coupled; activates phospholipase C, which releases IP3 and DAG
IP3 releases intracellular stores of Ca2+ and DAG activates PKC
Alpha 2 - Receptor Coupling
Gi protein coupled; inhibits adenylyl cyclase activity, decreasing cAMP levels and opening K+ channels to hyperpolarize the cell
B1 and B2 - Receptor Coupling
Gs protein coupled; stimulates adenylyl cyclase, increasing cAMP synthesis; cAMP activates PKA increasing Ca2+ movement into the cell through LTCCs
Sympatholytic action
Interference with adrenergic function in the presynaptic neuron; lack of specificity of action (all adrenergic synapses affected)
