11/2 SNS Review - Corbett Flashcards
location of cell bodies of postgang SNS
major postgang neurotransmitter
intermediolateral horn (L1-T3)
neurotransmitter: norepinephrine/epinephrine (or DA in some cases)
* EXCEPTION: Ach for sweat glands!
synthesis of endog catecholamines
in cytoplasm:
L-Tyr → LDOPA [tyrosine hydroxylase]
LDOPA → dopamine [L-aromatic a.a. decarboxylase]
transported into vesicles [vesicular monoamine transporter]
in vesicles:
dopamine → L-norepinephrine [dopamine-beta-hydroxylase, DBH]
which drug targets vesicular monoamine transporter?
reserpine!
conversion of norepi → epi
in adrenal medulla:
L-norepinephrine → L-epinephrine [phenylethanolamine-N-methyltransferase, PNMT]
- both NE and epinephrine stored in chromaffin granules in adrenal medulla (approx 80% epi)
- when adrenal medulla is stimulated, released
reuptake and metabolism of NE
depends on:
- reuptake into synaptic terminal
- affected by cocaine, TCAs
- metabolism of NE to inactive metabolite
- in mitochondria (MAO)
- at post-synaptic nerve (COMT)
- diffusion away from nerve terminal
norepi summary
two main classes of adrenergic receptors
alpha (a=alpha)
signalling depends on type of receptor subclass (alpha1 vs alpha2)
- a1A
- a1B
- a1D
- a2A
- a2B
- a2C
beta (b=beta)
all signalling via increase in cyclic AMP
- b1
- b2
- b3
alpha1 adrenergic receptors
what happens?
physio effects?
located on post-synaptic membrane
linked to G protein: Gq
activation of alpha1r →→→
- activation of phospholipase C
- formation of IP3 → increased Ca in cell!
- activation of protein kinase C (via DAG)
increase in cell Ca → activation of Ca-dependent protein kinase
effects:
1. increased smooth muscle contraction
- peripheral vasoconstriction → incr bp (alpha1b)
- incr systemic vascular resistance
- decr venous capacitance
- incr bp (systolic and diastolic) →→→ decr HR (baroreceptor effect: turns off sympathetic output from CNS)
- overall: MINIMAL effects on heart!
- urinary retention (alpha1a; non selective effects via a1B, a1D)
- mydriasis
- can increase pressure in anterior chamber of eye → exacerbates glaucoma!
alpha2 adrenergic receptors
what happens?
physio effects?
located on pre-synaptic membrane
linked to G protein (G-alpha-i)
inhibition of nt release (both NE and ACh)
effects:
1. autonomic nervous system modulation
- inhibition of NE release (via inhibitory autoreceptors)
- inhibition of Ach release (via inhibitory heteroreceptors)
2. inhibition of insulin release from pancreatic beta cells
3. agonists DECREASE aqueous humor production → effective for treating glaucoma!
beta adrenergic receptors
how do they work
effects at heart
locations/effects of beta1, beta2, beta3
all three lead to INCREASED LEVELS OF CYLIC AMP
- cAMP, in turn, acivates PKA
effects at heart:
- inotropy:
- activation of L-type Ca channels → incr Ca levels
- also via sarcoplasmic reticulum and incr NCX action
- phsophorylation of contractile proteins
- incr ATP availability
- chronotropy
* incr cAMP → affects If via incr HCN activity (If = funny current = phase 0, decreasing K permeability and slow Na entry = gradual depolarization)
beta1: postsynaptic
- in heart:
- incr contractility
- incr HR
- incr conduction
- in JGA (kidney):
- incr renin release
beta2: can be presynaptic (can create pos feedback loop!)
- in smooth muscle of periphery/bronchus
- bronchodilation
- vasodilation
- uterine relaxation
- in liver:
- increased glucose (via glycogenolysis and gluconeogenesis)
- in skeletal muscle:
- increased glucose (via glycogenolysis)
- decreased potassium (via K uptake)
beta3
- on adipocytes:
- increased lipolysis
beta1 receptors
locations/effects
beta1: postsynaptic
- in heart:
- incr contractility
- incr HR
- incr conduction
- in JGA (kidney):
- incr renin release
beta2 receptors
locations/effects
beta2: can be presynaptic (can create pos feedback loop!)
- in smooth muscle of periphery/bronchus
- bronchodilation
- vasodilation
- uterine relaxation
- in liver:
- increased glucose (via glycogenolysis and gluconeogenesis)
- in skeletal muscle:
- increased glucose (via glycogenolysis)
- decreased potassium (via K uptake)
beta3 receptors
locations/effects
beta3
- on adipocytes:
- increased lipolysis
how can you terminate beta receptor signalling?
beta receptor signalling can be terminated by PHOSPHORYLATION
- followed by internalization of P’d receptors
summary of major effects
