Pharm - Lecture 6 - overview nervous system Flashcards
What NT is released by Motor Nuerons?
acetylcholine
What NT reinforces sympathetic action? Where is it released?
epinephrine from adrenal medulla
What NT is released by pre-ganglionic Parasympathetic fibers?
acetylcholine
What NT is released by Post-ganglionic Parasympathetic fibers?
acetylcholine
What NT is released by Pre-ganglionic Sympathetic fibers?
acetylcholine
What NT is released by Post-ganglionic Sympathetic Fibers?
Mostly norepinephrine
Exception: acetylcholine is released by Sympathetic cholinergic fibers going to sweat glands
What is the rate limiting step for the synthesis of norepinephrine and dopamine?
tyrosine hydroxylase
What drugs is tyrosine the precursor of?
dopamine, norepinephrine, epinephrine
What is the role of vesicular monamine transporter 2? (VMAT2)
VMAT2 transports dopamine into vesicles where it is converted to norepinephrine
What transports dopamine into vesicles in the nerve terminal?
What blocks this?
Transporter: vesicular monamine transporter 2 (VMAT2)
reserpine blocks this
Where is norepinephrine synthesized?
In vesicles in the nerve terminal varicosities
How is norepinephrine taken back into the nerve terminal?
reuptake into nerve terminal by norepinephrine transporter (NET or uptake 1)
What drug blocks the reuptake of norepinephrine?
cocaine
What is cocaine’s mechanism?
blocks ruptake of norepinephrine in the synaptic cleft
How is epinephrine removed from the synaptic cleft? (3 ways)
1) norepinephrine transporter (NET - 87%)
2) diffusion (8%)
3) extraneuronal transporter (ENT - 5%)
What does extraneuronal transporter (ENT) do?
It uptakes norepinephrine into the post-synaptic cell
What enzymes are primarily responsible for the degradation of norepinephrine and epinephrine? (2)
Monamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
What does Monamine oxidase (MAO) do?
MAO oxidatively deaminates catecholamines
Where is monamine oxidase found in the cell?
Outer surface of mitochondria
Which cells is monamine oxidase found in? (3)
adrenergic nerve terminals
highest amounts in liver and kidney
How many and what are the isoforms of MAO?
MAO-A, MAO-B
What does catechol-O-methyltransferase (COMT) do?
transfers a methyl group to the 3-hydroxy position of the phenyl ring
Where in the cell is catechol-O-methyltransferase (COMT) found?
cytosol
Which cell types is COMT found in?
widely distributed with high levels in liver and kidney
not found in adrenergic neurons
How is intraneuronal norepinephrine not taken into storage granules metabolized?
monamine oxidase (MAO)
What is VMA?
VMA is the final metabolite of norepinephrine after it is initially metabolized by MAO
Secreted in urin
What is a biological marker in urine that reflects level of sympathetic drive (or catecholamine secreting tumors)?
concentration of VMA in the urin
What is the rate limiting step of acetylcholine synthesis?
choline is taken into the nerve terminal via NA+ dependent carrier
How is acetylcholine synthesized?
choline acetyl transferase synthesizes acetylcholine from acetyl-CoA and choline
Where is acetylcholine synthesized?
nerve terminals
How is acetylcholine released from the nerve terminal?
acetylcholine is transported into a vesicle and exocytosed
What inhibits acetylcholine release into the synaptic cleft?
botulinum toxin
What is the mechanism of botulinum toxin?
inhibits the release of acetylcholine into the synaptic cleft
How is acetylcholine metabolized?
acetylcholinesterase
What is the major class of receptors for Acetylcholine?
cholinergic receptors
What is the major class of receptors for Norepinephrine?
Adrenergic receptors
What are the types of cholinergic receptors?
Nicotinic and Muscarinic
What are the types of Nicotinic receptors? (3)
Ganglionic, Skeletal muscle, Neuronal CNS
What are the types of Muscarinic receptors?
M1, M3, M5,
M2, M4
What type of receptor is the Nicotinic receptor?
It’s a Ligand-gated ion channel
What type of receptor is located aat the Neuromuscular junction?
Muscle Nicotinic receptor
What type of receptor is located at the Autonomic ganglia?
Peripheral Neuronal or ganlionic Nicotinic receptor
What receptor is at the adrenal medulla?
Peripheral neuronal or ganlionic Nicotinic receptor
What is the response when a Muscle Nicotinic receptor is activated?
end plate depolarization and skeletal muscle contraction
What is the response to an activated ganglionic nicotinic receptor?
At ganglia?
At adrenal?
at ganglia: depolarization and firing of post ganglionic neuron
adrenal: depolarization of chromaffin cells and secretion of catecholamines
What type of receptor are Muscarinic receptors?
G-protein couple receptors
What type of G protein is associated with an M2 Muscarinic receptor?
Gi
What type of G protein is associated with an M3 Muscarinic receptor?
Gq
Where are M2 Muscarinic receptors located? (3)
Heart, nerves and smooth muscle
Where are M3 Muscarinic receptors located? (3)
glands, smooth muscle, endothelium
What is the response of an activated M2 muscarinic receptor?
decrease electrical conduction and therefore decreases in muscle contraction
What is the response of an activated M3 muscarinic receptor?
glands?
smooth muscle?
Increase secretion in glands
increase muscle contraction
What are the types of Adrenergic receptors?
alpha and beta
What are the types of alpha adrenergic receptors?
alpha1 and alpha2
What are the types of beta adrenergic receptors?
beta1, beta2, beta3
What type of G protein does the alpha1 adrenergic receptor activate?
Gq
What type of G protein is associated with the alpha2 adrenergic receptor?
Gi
What type of G protein is associated with the beta1 adrenergic receptor?
Gs
What type of G protein is associated with the beta2 adrenergic receptor?
Gs
What is the general location of the alpha1 adrenergic receptor? (2)
What is their response?
1) Vascular and other smooth muscles: contraction
2) Glands: secretion
What is the general location of the alpha2 adrenergic receptor? (3)
What is their response?
1) Nerve Terminals: Decrease NE release
2) Glands: decreased secretion
3) Vascular smooth muscle: contraction
What is the general location of the beta1 adrenergic receptor? (2)
What is their response?
1) cardiac muscle: Increased force and rate of contraction
2) glands: increased secretion
What is the general location of the beta2 adrenergic receptor? (3)
What is their response?
1) Vascular and other smooth muscle: Relaxation
2) skeletal muscle: glycogenolysis
3) liver: glycogenolysis and gluconeogenesis
Effector organ: SA node of the heart
Effect: Increase heart rate
Receptor?
B1
Effector organ: Atria of the heart
Effect: Increase contractility and conduction velocity
Receptor?
B1
Effector organ: AV node His-Perkinje system
Effect: Increase in automaticity and conduction velocity
Receptor?
B1
Effector organ: Ventricles of heart
Effect: Increase in contractility and conduction velocity
Receptor?
B1
Effector organ: Arterioles
Effect: Constriction
Receptor?
a1
Effector organ: blood vessels of skeletal muscle
Effect: Constriction
Receptor?
a1
Effector organ: Blood vessels of Skeletal muscles
Effect: dilation
Receptor?
B2
Effector organ: Veins
Effect: Vasoconstriction
Receptor?
a1
Effector organ: Bronchial smooth muscle
Effect: Relaxation
Receptor?
B2
Effector organ: Uterus
Effect: Relaxation
Receptor?
B2
Effector organ: Uterus
Effect: contraction during pregnancy
Receptor?
a1
Effector organ: GI tract - Motility and tone
Effect: Decrease
Receptor?
a2, B1, B2
Effector organ: GI tract - sphincters
Effect: Contraction
Receptor?
a1
Effector organ: GI tract - Secretions
Effect: Inhibition
Receptor?
A2
Effector organ: Eye - Radial muscle of iris
Effect: Contract (mydriasis)
Receptor?
a1
Effector organ: Eye - Ciliary muscle
Effect: No effect/slight relaxation
Receptor?
B2
Effector organ: Eye - Lacrimal glands
Effect: Secretions
Receptor?
a
Effector organ: Eye - Aqueous humor
Effect: Secretion
Receptor?
B
Effector organ: Kidney
Effect: Renin secretion
Receptor?
B1
Effector organ: Urinary bladder - Detrusor
Effect: Relaxation
Receptor?
B2
Effector organ: Urinary bladder - Trigone and sphincter
Effect: Contraction
Receptor?
a1
Effector organ: Sex organs: male
Effect: vas deferens contraction (ejaculation)
Receptor?
a1
Effector organ: Fat cells
Effect: Lipolysis
Receptor?
B1, B2, B3
Effector organ: Pancreas
Effect: Decrease insulin secretion
Receptor?
a2
Effector organ: Liver
Effect: Increase glycogenolysis and gluconeogensis
Receptor?
a1 and B2
Effector organ: Skeletal muscle
Effect: Glycogenolysis
Receptor?
B2
Effector organ: Salivary glands
Effect: Increase secretion
Receptor?
a1
Effector organ: Sweat glands
Effect: General secretion
Receptor?
M2 and M3
Effector organ: Sweat glands
Effect: Localized secretion
Receptor?
a1
Effector organ: SA node of heart
Effect: Decrease heart rate
Receptor?
M2
Effector organ: Atria of heart
Effect: Decrease contractility
Receptor?
M2
Effector organ: AV node His-Perkinje system of heart
Effect: Decrease conduction velocity; AV block
Receptor?
M2
Effector organ: Bronchial smooth muscle of lung
Effect: Contraction
Receptor?
M2 and M3
Effector organ: Bronchial glands of lung
Effect: Stimulation
Receptor?
M2 and M3
Effector organ: Gi tract - Motility and tone
Effect: Increase
Receptor?
M2 and M3
Effector organ: GI tract - Sphincters
Effect: Relaxation
Receptor?
M2 and M3
Effector organ: GI tract - Secretions
Effect: Stimulation
Receptor?
M2 and M3
Effector organ: Eye - Sphincter muscle of iris
Effect: Contract (miosis)
Receptor?
M2 and M3
Effector organ: Eye - Ciliary muscle
Effect: Contract (near vision)
Receptor?
M2 and M3
Effector organ: Eye - Lacrimal glands
Effect: Secretion
Receptor?
M2 and M3
Effector organ: Urinary bladder - detrusor
Effect: Contraction
Receptor?
M3 > M3
Effector organ: Urinary bladder - Trigone and sphincter
Effect: Relaxation
Receptor?
M3 > M2
Effector organ: Sex organs: male
Effect: Erection
Receptor?
M3
Effector organ: Pancreas
Effect: Increase secretion by acini
Receptor?
M2 and M3
Effector organ: Nasal
Effect: Secretion
Receptor?
M3
Effector organ: Salivary glands
Effect: Increase secretion
Receptor?
M2 and M3
What is the synthetic pathway starting from tyrosine and ending in epinephrine?
Tyrosine –> DOPA –> Dopamine –> norepinephrine –> epinephrine (last step in adrenal medulla)