Autonomics - Basics Flashcards
What is the division between sympathetic and parasympathetic?
difference is anatomical in origin
sympathetic - thoracolumbar
parasympathetic - craniosacral
Where are the ganglia of the sympathetic NS? Length of pre vs post-ganglionic neurons?
Ganglia in paravertebral chains; pre ganglionic fibers tend to be short and post ganglionic long
Where are ganglia of parasympathetics? Length of fibers?
Ganglion cells distributed diffusely or in networks in walls of innervated organs. Long pre-ganglionic, short post-ganglionic
What NT is used in all ganglia?
Ach
What NT is used by post-ganglionic parasympathetics?
Ach - cholinergic
What NT is used by most post-ganglionic sympathetics?
NE - adrenergic
What are the three exceptions in the sympathetic nervous system?
sweat glands, renal vascular smooth muscle, and chromaffin cells in adrenal medulla
What NT is used by sympathetics going to sweat glands?
Ach
What NT is used by sympathetics going to renal vascular smooth muscle?
dopamine
What happens with sympathetics going to the adrenal medulla?
Pre-ganglionic releases Ach on chromaffin cells which acts as specialized post-ganglionic neurons and release epi and NE into the blood
Which branch of the ANS is more diffuse and which is more discrete?
Sympathetic - diffuse
parasympathetic - discrete
Where is the enteric nervous system located?
walls of the GI tract
What three things does the enteric nervous system receive input from?
preganglionic parasympathetics, postganglionic sympathetics, sensory input from within the wall of the gut
Where is the output of the enteric nervous system directed? What does it affect?
To smooth muscle and secretory cells to control motility and secretion
What’s the result of ligand binding to nicotinic receptors? How do the Nn and Nm differ?
differ in subunit composition (and sometimes in how many ligand binding sites);
ligand binding results in opening of Na and K channels and depolarization
What’s the mechanism of M2 and M4 receptors?
Gi; inhibit adenylate cyclase and/or activate K channels (hyper polarization)
hyperpolarization of M2 causes slowing of heart, inhibition of neurotransmitter release
What’s the mechanism of M1, M3, and M5 receptors?
Gq; activate phospholipase C, increasing DAG and IP3 (therefore Ca2+)
smooth muscle contration by M3
neuroregulation by M1
What’s the mechanism of alpha-1 receptor?
Gq; activate PLC, leads to smooth muscle contraction
What’s the mechanism of alpha-2 receptors?
Gi; decrease cAMP, hyperpolarize via K channel; leads to inhibitions of neurotransmitter release
What’s the mechanism of the beta receptors?
all Gs; activate adenylate cyclase and increase cAMP
beta-1 - increase in force and rate of heart
beta-2 - smooth muscle relaxation
beta-3 - increase lipolysis
Autoreceptors are often used in presynaptic regulation. Are they generally excitatory or inhibitory?
inhibitory; inhibit further release of that NT
What are receptors on the presynaptic terminal that respond to NT other than that released by that neuron and exert control on NT release called?
heteroreceptors
What are possible sites of therapeutic opportunity?
NT synthesis, storage, release, termination
receptors on postsynaptic cells
What are the steps in the synthesis of catecholamines? Note important locations where appropriate.
tyrosine -> L-DOPA (rate-limiting step)
L-DOPA -> dopamine
dopamine -> norepi (occurs in vesicles)
norepi -> epi (in adrenal medulla)
Differences in norepi and epi.
norepi = neurotransmitter; action in synapse epi = neurohormone; released into vasculature by adrenals to have effect
What are the three ways that norepi effect is terminated?
Uptake 1 - ‘re-uptake’ neuron specific, high specificity, low capacity
Uptake 2 - extra-neuronal (ie by effector cell); non-specific, high capacity; how most drugs will be processed
Diffusion away into capillaries, etc
Uptake 1 is the primary mechanism!!! Uptake 2 is a lesser role
What are the major metabolic enzymes for epi and norepi? Where are they located?
MAO - monoamine oxidase; located on mitochondria surface
COMT - catechol-O-methyl transferase; located in cytoplasm of many cells, notably liver
Agonist (ISO, Epi, NE, DA, CLON) at adrenergic receptors.
beta1 - ISO>Epi>=NE>DA
beta2 - ISO>Epi»NE»DA
alpha1 - Epi>=NE>DA»ISO
alpha2 - CLON>Epi>=NE»ISO