Autonomic Pharmacology Flashcards
Branches of the Autonomic nervous system
PSNS and SNS branches
PSNS vs SNS
PSNS = rest and digest
SNS = fight or flight
- most organs receive input from both (blood vessels and some glands are exceptions)
- mediate opposing responses - physiological antagonists
what are exceptions for organs that only recieve input from the SNS or PSNS, not both
PSNS = lacrimal gland
SNS = blood vessels, sweat glands, skin (pilomotor SM)
where do parasympathetic and sympathetic nerve fibres originate from
PSNS = upper and lower spinal cord (cranial, cervical and sacral)
SNS = middle spinal cord (thoracic and lumbar)
the 2-neuron system of the PSNS and SNS
- contain pre and post ganglionic fibers
- preganslionic neurons send signak from the CNS to the canglion
- postganglionic neurons send axons to the target tissue
what is a ganglia
an aggregation of cell bodies of postganglionic neurons
what is the difference in ganglia locations between the SNS and PSNS
SNS: ganglia are near the spinal cord, one preganglionic to many post ganslionic fibers
PSNS: ganglia are near the target tissue, one preganglionic to onw postganglionic fiber
autonomic nerves are classified basses on the neurotransmitters they release…
cholenergic neurons = release ACh
adrenergic neurons = release EP (or NE)
cholinergic neurons
release ACh
Adrenergic neurons
release EP or NE
which organ secretes EP instead of NE for adrenergic neurons
the adrenal glands
Sweat glands as an exception to SNS neurotransmitters
- ganglia release ACh instead of NE even tho it it in the SNS
neurotransmitters resleased by each neuron in the SNS
preganglionic = ACh at nicotinic receptor
post ganglionic = NE ar adrenergic receptor (alpha or beta)
neurotransmitters released by each neuron in the PSNS
preganglionic = ACh at nicotinic receptor
post ganglionic = ACh at muscorinic receptor
types of cholenergic receptors
Muscarinic (M1-M5)
Nicotinic (NN and NM)
where are the different type of nicotinic receptors found in
NN: all ganglia - neurons (PSNS and SNS)
NM: skeletal muscle (somatic NS - voluntary)
adrenergic receptor subtypes
alpha (a1 and a2) - activated by NE and EP
beta (B1, B2, B3) - EP»NE
what does the B1 adrenergic receptor stimulate
the heart
what does the a1 adrenergic receptor stimulate
blood vessel constriction
neurotransmitter and receptor pairs found in cardiac muscle
ACh x M2
NE x B1
how is ACh made and degrades
made by acetyltrancferase (ChAT)
degraded by acetylcholinesterase (AChE)
which receptors does ACh activate
muscorinic (M1-5) - via GPCR’s
nicotinic (Nn and Nm) - via ion channels
which ACh receptors are stimulatory
M1, M3, M5, Nn, Nm
which ACh receptors are inhibitory
M2, M4
how are M1, M3, and M5 stimulatory
they increase the production of IP3 and DAG
how are M2 and M4 inhibitory
they decrease cAMP production
what happens at the cholenergic synapse
- ChAT makes ACh
- action potential initiates influx of Ca2+ to cause release of ACh
- ACh in synaptic cleft can binf to N or M receptors on postsynaptic cells
- excess ACh is degraded by AChE into Choline and Acetate
- Choline can be recycled via charrier protein
where in the body are M2 receptors found and what is their effect
the heart - decrease rate and foce of contraction
where in the body are M3 receptors found and what is their effect
smooth muscles - contraction
glands - increase secretion
endothelial cells - increase EDRF release
how do M1, M3 and M5 cause their excitatory effects
- agonist binds M receptor
- G-protein is activated which activates PLC
- PLC cleaved to PIP
- PIP causes activation of IP3 and DAG
- IP3 activates calcium-dependent protein kinases and DAG activates PKC
how do M2 and M4 cause their inhibitory effects
- agonist binds M receptor
- G-protein is activated which casues inhibition of adenylate cyclase
- cAMP production is inhibited and therefore decreases activity of the cell
Affects of ACh and cholenergic receptors in blood vessels
- blood vessels only receive SNS input (no PSNS)
- cholenergic receptors are still present on blood vessel endothelial cells but no ACh is sent here natually
what happens when a muscarinic agonist binds M3 receptors in blood vessels
- produces the endothelial derived relaxing factor (NO)
- NO activates guanylyl cyclase to produce cGMP
- relaxation of the smooth muscle
nicotinic receptor (Nn) locations and effects
postganglionic neurons = excitation
adrenal gland = secretion
CNS = excitation
nicotinic receptor (Nm) locations and effects
skeletal muscle = contraction
structure of nicotinic receptors
- receptor subunits come together to make the ion channel
- some subunits have binding sited for ACh (alpha subunits)
- when ion influx = depolarization, secretion or contraction
3-step synthesis of norepinephrine
- tyrosine hydroxylase
- dopa decarboxylase
- dopamine B-hydroxylase - makes NE
norepinephrine termination
reuptaken or diffusion away from the synapse
norepinephrine metabolism
metabolized by MAO and COMT
what happens at the Noradrenergic synapse
-Tyr brought to presynaptic cell by carrier protein
- Tyr converted to DOPA then dopamine then NE in vesicles
- action potential initiates Ca2+ influx to release NE into synapse
- NE can be reuptaken by presynaptic cell via active transport (then metabiolized by MAO)
- NE can be uptaken by postsynaptic cell via passive diffusion (then metabolized by COMT)
whcih adrenoceptors are present on on postsynaptic vs presynaptic cells
pre = a2 (inhibitory)
post = a1, B1, B2 (excitatory)
basics of adrenergic transmission
- dopamine is transported into synaptic vesicles and converted to NE by B-hydroxylase
- epinephrine is secreted by the adrenal medulla and circulates via blood to various tissues
- adrenoceptors are linked to GPCRs
effects of alpha and beta adrenoceptors
a1: activates IP3 and DAG (same as M1,3,5)
a2: inhibits cAMP (same as M2,4)
B1 and B2: activtes cAMP
how to B1 and B2 (+B3) cause their excitatory effetcs
-agonist binds B receptor
- activated G protein
- activated adenylate cyclase to produce cAMP
enzyme phosphorylation can occur
location and action of a1 receptors
smooth muscle = contraction
- blood vessels
- eye
- pilomotor
- sphincters
location and action of a2 receptors
SNS nerve terminals = decreased NE
PSNS nerve terminals = decreased ACh
beta receptors location and action
B1: heart = increased rate and force of contraction
B2: smooth muscle cells (many organs) = relaxation
B3: fat cells = increased lipolysis
which muscles of the eye are controlled by the different branches of the nervous system
sphincter (constriction) = PSNS = M3 receptors
Dialator (dialation) = SNS = a1 receptors
what controls if the pupil constricts vs. dialates
constricts = contraction of the spincter when ACh binds to M3 receptor
dilates = contraction of the dialator when NE binds to a1 receptor
how is intraocular pressure of the eye determined
- by the amount of aqueous humor in the eye
- removal of fluid: contraction of the ciliary muscle (M3) causes drainage through canal
- production of fluid: alpha-receptors casue decresed secretion, Beta-receptors cause increased secretion
effects of direct-acting receptor agonists on the heart
M2-receptor agonist = decreased heart rate
B1-receptor agonist = increased heart rate
effects of direct-acting receptor agonists on most blood vessels
M3-receptor agonist = vasodialation (relax)
a1-receptor agonist = vasoconstriction (contract)
effects of direct-acting receptor agonists on blood vessels in skeletal muscle
B2-receptor agonist = vasodialation (relax)
effects of direct acting receptor agonists on most organ systems/glands
M3-receptor agonists = contraction (increased activity in organs + increased secretion in glands)
B2-receptor agonists = relaxation od smooth muscle lining organs
a1-receptor agonists = constriction of sphincters (e.g. decrease urination)
autonomic transmission can be inhibited or stimulated by chemicals (drugs) that affect…
- neurotransmitter synthesis
- neurotransmitter storage
- neurotransmitter release
- receptor activation
- neurotransmitter re-uptake or inactivation
what similar physiological response in cardiac muscle (decreased rate and force of contraction) can be caused by different drugs
- Muscarinic agonists bind M2 casue ACh accumulation (PSNS)
- AChE inhibiter causes ACh accumulation (PSNS)
- B1 blocker (antagonist) prevents NE from binding receptor (SNS)
