Autonomic pharmacology Flashcards
Parasympathetic nervous system
“rest and digest”
Sympathetic nervous system
“fight or flight”
PSNS and SNS mediate opposing responses in effector organ, they are known as
Physiological antagonists
Where does the PSNS begin
Cranial and sacral spinal cord
Where does the SNS begin
Thoracic and lumbar spinal cord
“2-neurons system”
pre- and postganglionic fibers
Ganglia
aggregation of cell bodies of postganglionic neurons
Where is the ganglia in SNS and give details on the pre and postganglionic fibers
-Ganglia near spinal cord (short preganglionic and long post-ganglionic fibers)
-One preganglionic to many postganglionic fibers
Where is the ganglia in PSNS and the give details on the pre and postganglionic fibers
-Ganglia close to or within target tissue (long preganglionic and short postganglionic fibers)
-One preganglionic to one postganglionic fiber
Autonomic nerves classified based on
neurotransmitters
What do cholinergic neurons release
Acetylcholine (ACh)
What do most postganglionic SNS neurons release
Norepinephrine (NE)
Adrenal gland secretes
Epinephrine (EP)
EP is also known as
Adrenaline (therefore neurons referred to as adrenergic)
Cholinergic autonomic receptors and their subtypes
- Muscarinic (M1, M2, M3, M4, M5)
2.Nicotinic (NN, NM)
Muscarinic,: which receptor sub types correspond with organs innervated by PSNS
M2, M3
Muscarinic,: which receptor sub-types correspond with endothelial cells
M3, M5
Muscarinic: which receptor sub-types correspond with sweat glands innervated by cholinergic SNS fibers
M3
Muscarinic: which receptor sub-types correspond with some ganglia
M1
Muscarinic: which receptor sub-types correspond with the CNS
All
Nicotinic: where is NN found
In the ganglia (PSNS and SNS)
Nicotinic: where is NM found
On skeletal muscle (somantic nervous system)
Adrenergic autonomic receptors are found where
In organs innervated by SNS and in CNS
How are alpha and beta receptors activated
-Alpha activated by NE and EP
-Beta activation of B2 EP»>NE
Adrenergic autonomic receptors and their subtypes
- Alpha (a1, a2)
- Beta (B1,B2,B3)
What causes alterations in the balance of neurotransmitters
Autonomic drugs, stress, environmental input
In most tissues PSNS and SNS are considered to be
physiological antagonists
Which receptors are activated by acetylcholine (sympathetic)
(start with SHORT preganglionic fibers) Nicotinic receptor, (now post-ganglionic fibers), norepinephrine, adrenergic receptors
Which receptors are activated by acetylcholine (parasympathetic)
(start with LONG preganglionic fibers), nicotinic receptors, (now postganglionic fibers), muscarinic receptor
Presynaptic pathway
- Action potential in presynaptic fiber
- Synthesis of transmitter
- Storage
- Metabolism
- Release
- Uptake
- Degredation
Postsynaptic pathway (following presynaptic)
- Receptor binding
- Receptor stimulation
- Response
Cholinergic transmission is synthesized by
the enzyme choline
acetyltransferase (ChAT)
Cholinergic transmission is degraded by
enzyme
acetylcholinesterase (AChE)
Cholinergic transmission is driven by
Acetylcholine
Acetylcholine activates which receptors
Muscarinic
Cholinergic transmission: affect on increase IP3 and DAG
stimulatory
Cholinergic transmission: affect on decrease in cAMP
inhibatory
Adrenergic: _____ and ______ determine tissue response
Location and subtype
Odd number (1, 3, 5) Muscarinic receptors correspond to _______ G proteins
Stimulatory
Even number (2.4) Muscarinic receptors correspond to ______ G proteins
Inhibatory
Nicotinic receptors correspond to
Stimulatory ion channels
M1 location and action
Some autonomic ganglia, raise activation
M2 location and action
Heart, lower rate/force of contraction
M3 location and action
Smooth muscle, Glands & Endothelial cells, Contracts, raise secretion & raise EDRF release
M5 location and action
Endothelial cells, raise EDGF release
M1, M3, M5 pathway
-Agonist binds to rec & activates it
-Activated G protein
-Activates phospholipase C
-Phospholipase C cleaves PIP2 to IP3
-[DAG activates PKC]
-IP3 releases stored calcium to give free calcium
-Activated calcium-dependant protein kinases
M2 & M4 pathway
-Agnoist binds to receptor and activates it
-Activated G protein
-Inhibits adenylate cyclase
Adenylate cyclase would normally do what (pathway)
-Uses ATP to produce cAMP
-cAMP goes to protein kinase
-Phosphorylates enzyme
There is no PSNS input to blood vessels but…
Cholinergic receptors are present on endothelial cells that line the blood vessels (direct agonists relax vascular smooth muscle)
EDRF
Endothelial derived relaxing factor (nitric oxide)
Endothelial M3 receptor path
Muscarinic agonist binds rec –> Raise Ca2 –> NO –> Ganylyl cyclase –> Raise cGMP
NN location and effect
-Postganglionic neurons [excitation]
-Adrenal glands
[secretion]
-CNS
[excitation]
NM location and effect
Skeletal muscle [contraction]
Nicotinic receptor sub-units make up
Ion channels (Na+/K+)
Noreprinephrine 3 step synthesis
1)Tyrosine hydroxylase
2) Dopa decarboxylase
3) Dopamine -hydroxylase
Norepinephrine termination
1) Re-uptake
2) Diffusion away from synapse
Norepinephrine metabolized by
Monoamine oxidase (MAO) and catechol- O-methyl transferase (COMT)
Review synapses
ya
Adrenergic transmission
-Dopamine transported into synaptic vesicles and converted to NE by Beta-hydroxylase
-Epinephrine secreted by adrenal medulla – circulates via blood to various tissues
Adrenoreceptors
1.Alpha
a1 = same as M1,M3,M5
a2 = same as M2,M4
2.Beta
B1,B2,B3 = raise cAMP
B1,B2,B3 receptor pathway
-Agonist binds to receptor and activates it
-Activated G protein
-Activates adenylate cyclase
-ATP to cAMP
-Protein kinase phosphorylates enzyme
Alpha 1 receptor location and action
Smooth muscle cells, [contraction]
Where specifically are alpha 1 receptors located
-blood vessels (supplying organs and skin
-eye
-pilomotor sm.muscle
-sphincters (GI and urinary)
Alpha 2 location and action
-SNS nerve terminals: [lower NE]
-PSNS nerve terminals (high in GI tract) [lower ACh]
Beta 1 receptors location and action
Heart [raise rate/force of contraction]
Beta 2 location and action
Smooth muscle cells (relaxation)
-bl. vessels {supply skeletal muscle], bronchial tree, uterine,GI & bladder walls)
Beta 3 location and action
Fat cells [raise lipolysis]
Contraction of sphincter: by which receptor and what affect on pupil
M3, constriction of pupil
(Release ACh)
Contraction of dilator: by which receptor and what affect on pupil
alpha 1, dilation of pupil
(Release NE)
Aqueous humour removal
-Contraction of cilinary muscle (M3) = higher drainage
Aqueous humour production
alpha - decrease secretion
beta - increase secretion
Herat rate
M2 - decrease
B1 - increases
Blood vessels (most)
M3 - vasodilation
a1 - vasoconstriction
Blood vessels (sk. muscle)
B2 - vasodilation
Most organ systems/glands
M3 –> contraction –> increase activity –> increase secretion
B2 –> relaxation of smooth muscle
a1 –> constriction of sphincters
Autonomic transmission can be inhibited or
stimulated by chemicals that affect
*Neurotransmitter synthesis
*Neurotransmitter storage
*Neurotransmitter
release
*Receptor activation
*Neurotransmitter re-uptake
or inactivation
