Introduction to Autonomic Pharmacology Flashcards
(138 cards)
1
Q
What are the two branches of the human nervous system?
A
the central nervous system and the peripheral nervous system
1
Q
What are the two parts the central nervous system?
A
the brain and the spinal cord
1
Q
What are the two divisions of the peripheral nervous system?
A
the somatic and the autonomic nervous system
1
Q
What are the differences between the skeletal and autonomic nervous system?
A
the skeletal nervous system controls voluntary movement while the autonomic nervous system operates on its own
1
Q
How does the peripheral nervous system work?
A
the peripheral links the CNS with the body’s sense receptors, muscles and glands–response elicited in effector organs by specific chemical neurotransmitters
1
Q
What is the ANS?
A
a motor division of the peripheral nervous system
1
Q
How is the ANS controlled?
A
controlled by the hypothalamus and other regualatory and reflex center in the CNS
1
Q
What is the main function of ANS?
A
regulates individual organ function and homeostasis and is not subject to voluntary control
1
Q
What are some other names for the ANS?
A
general visceral motor system
involuntary nervous system
autonomic nervous systerm
1
Q
What is afferent information? How is it transmitted?
A
sensory input from the viscera (organ itself)—-> the central nervous system
examples of sensory input:
- drop in blood pressure
- reduced stretch of baroreceptors in aortic arch
- reduced frequency of afferent impulses to medulla (brainstem)
1
Q
What is the reflex response/ efferent reflex?
A
its a reflex response; from the autonomic nervous system—-> to the organ etc
examples of reflex response:
- inhibition of parasympathetic and activation of sympathetic divisions
- increased peripheral resistance and cardiac output
- increased blood pressure
1
Q
Give some examples of the function of ANS?
A
most controls the stability of the internal environment to maintain homeostasis:
examples:
- shunts blood as needed
- control heart and respiratory rate
- adjust blood pressure and body temperature
- controls gastrointestinal (GI) tract secretions
1
Q
What are main anatomical divisions of the ANS?
A
sympathetic
parasympathetic
enteric nervous system
1
Q
How does information get relayed in the anatomical divisions of the ANS? and what is the exception?
A
conveys all the outputs from the central nervous sustem to the rest of the body (the periphery)
the exception is the motor innervation of skeletal muscle which is innervated by the the somatic nervous system
1
Q
How wide spread is the ANS?
A
it reaches almost every part ofthe body and influnces (directly or indirectly) every organ system
1
Q
Summarize the division of the peripheral nervous system.
A
the peripheral nervous system:
- parasympathetic (PSNS)
- symptathetic (SNS)
- somatic
1
Q
What are afferent sensory neurons?
A
carriers nerve impulses toward the brain
1
Q
What is the CNS?
A
central nervous system comprising the brain and the spinal cord
1
Q
What are efferent (motor) neurons?
A
carry nerve impulses away from the brain
1
Q
What is motor neuron?
A
mortor refers to neural structures which generate impulses and transmit impulses to cause muscle fiber or pigment cells to contract or glands to secrete
1
Q
What is ganglia?
A
clusters of nerve cells
1
Q
What are autonomic effector cells?
A
the cells which execute efferent neural commands
examples:
- cardiac muscle cells
- smooth muscle cells
- gland cells
Autonomic effectors are spontaneously active and the autonomic inputs facilitate or inhibit ongoing effector activity
1
Q
What are the important anatomical divisions of of the spinal cord?
A
the brain
spinal cord
conus medullaris
cauda equina
1
Q
What are the 5 nerve divisions of the spinal cord and how may nerves are in each section?
A
cervical area- 8 cervical nerve
thoracic area- 12
lumbar area- 5
sacral area- 5
coccygeal area
1
What organs does the sympathetic system innervate?
innervate organs, secretory glands, etc.
1
Where are preganglionic neurons and ganglion found in the sympathetic nervous system ?
preganglionic neurons arise in spinal cord; ganglion close to spinal cord--short preganglionic
1
What organs does the parasympathetic nervous system innervate?
innervates less structures than the syspathetic
1
Where the the preganglionic and ganglia located in the parasympathetic nervous system?
preganglionic neurons arise in midbrain and spinal cord sacral area ---\> they synapse on the ganglia close or within structures innervated
1
PNS: Where does nerve\_\_\_\_ innervate? 1) III 2) VII 3) IX 4) X 5) Sacral region
1) III----\> ciliary muscle of eye
2) VII-----\> salivary gland
3) IX----\> salivary gland
4) X----\> heart, trachea & lungs, pancrease, kidney, small & large intestines
5) sacral region------\> large intestine, urinary bladder, gonads, and genitalia
1
What is the parasympathetic nervous system also known as?
craniosacral outflow
1
What are the thoracic links to?
the internal organs, as well as, the sweat glands, hair follicles and blood vessels of the torso
1
What organs are regulated by the ANS?
1) heart
2) lungs
3) blood vessels
4) liver
5) fat depots
6) exocirne glands
7) the gastrointestinal tract
8) adrenal medulla
9) kidney
10) ureter
11) bladder
12) sex organs
13) skin
14) eyes
1
What functions are regulated by the ANS?
1) heart rate
2) blood pressure
3) regional blood flow
4) breathing
5) cellular metabolism
6) gastrointestinal motility
7) secretion exocrine glands
8) body temperature
9) emptying of hollow viscera--in short, housekeeping chores within the boyd
1
How can housekeeping chores within the body be controlled?
these functions are usually involuntary but one can learn to control them consciously (eg. with yoga, meditation)
1
Although SNS and PNS serve the same organ what is the difference in their function and why is this important?
yes, the SNS and PNS serve the same visceral organ but quite often causes opposite effects
1
What types of activities can PSN and SNS work to create? Give examples
dynamic antagonism between the two divisions, fine adjustments are made continously by both---activity is an integration of both divisions
the actvities of the PSNS and the SNS on specific structures may be either
1) discrete and independent
2) integrated and interdependent
Example:
the heart and iris functional antagonism exists in controlling heart rate and pupillary aperature
the actions on male sex organs are complementary and integrated to promote sexual function
control of peripheral resistance is discrete and primarily due to sympathetic control of arteriolar resistance
1
Describe the autonomical features of the autonomic nervous system?
consiste of two motor neurons in series---these are called the preganglionic and postganglionic neurons
synapse in an autonomic ganglion which lies outside of the CNS----\> autonomic ganglion contains the nerve endings of the preganglionic fibers and the cell bodies of postganglionic fibers
1
What is the role of the parasympathetic division? and how is it organized?
Digestion and maintenance activities--essential for life; D division: digestion, defecation, an d diuresis (urination)---Rest and Digest!
-organization mainly discrete and localized discharged
1
What is the role of sympathetic division and how is it organized?
adjust to a constantly changing environment; F division: fight, flight, and fright
it will discharge as a unit, in particular during emergency or life threatening situations
1
Give an example of sympathetic action.
though active to some degree, it is during vigorous physical activity the SNS will cause increase blood flow to skeletal muscles and the heart, dilation of the bronchioles in the lungs and pupils of the eyes, release glucose by the liver, inhibition of GI activity
1
Why is the parasympathetic output considered discrete and the sympathetic output considered diffuse?
the sympathetic output is diffuse because postganglionic neurons may integrate more than one organ
parasympathetic is discrete because postganglionic neurons are not branched but are directed to a specific organ
1
What is the cholinergic and adrenergic portion of the ANS?
the cholinergic portion is included in the parasympathetic system
the adrenergic portion in sympathetic
1
Explain what the sympathetic nervous system does to the: 1) eye 2) salivary gland 3) heart and lungs 4) gastric and pancreatic 5) gall bladder 6) digestive tract 7) adrenal gland 8) excretory and reproductive organs
1) Eye:
contraction of the iris radial muscle (pupil dilates)
contraction of the iris sphincter muscle (pupil contracts)
contracts of ciliary muscle (lens accomadation for near vision)
2) salivary glands:
inhibits secretion
3) heart & lungs:
heart:
through B1 accelerates heart rate
vessels:
through B2 dilates
through A1 constricts
lungs:
through B2 dilates bronchi
4) gastric and pancreatic:
inhibits activity
5) gallbladder:
stimulates glucose release
6) GI tract :
inhibits activity of GI motility and secretion
7) adrenal gland:
stimulate adrenal secretion
8) excretory and reproductive organs:
B2 relaxes bladder
A1 constricts sphincter
1
Explain what the parasympathetic nervous system does to the: 1) eye 2) salivary gland 3) heart and lungs 4) liver 5) gall bladder 6) stomach 7) digestive tract 8) excretory and reproductive organs
1) eye:
contracts pupil
2) salivary gland:
stimulating secretion of lacrimal and salivary glands
3) heart and lungs:
heart:
slows heart rate
lungs:
contracts bronchi
4) gastric and pancreatic activity:
1
Explain the structure of efferent pathways in the somatic division of PNS?
cell bodies of motor neurons are in the central nervous system and the acon extend to muscles served--the axons are highly branched and innervate a single muscle
the neurons are myelinated for fast conduction of impulses and not they completely lack ganglia
1
What do the nerve ending of somatic nerve release and what are their receptors?
release acetylcholine
1
Explain the sturcture of efferent pathways in the autonomic division of the PNS?
irs a two neuron chain between the central nervous system and the effector
first there is a preganglionic neuron--its cell body resides in the central nervous system (which is the brain or spinal cord)
this synapses on the-----\>MOTOR ganglion which is outside the CNS
the POSTGANGLIONIC NEURON, the cell body resides in the ganglion----\> the UNMYELINATED axon extends to the EFFECTOR ORGAN
This is a slow conductance of impulses.
1
Explain the neurotrasmitter effects of somatic division?
all somatic neurons release acetylcholine at their synapase and the effect is excitatory
1
Explain the neurotramitter effects of the autonomic division?
all preganglionic neurons release ACh
postganglionic autonomic fibers release:
1) norepinephrine if they are sympathetic
2) acetylcholine if they are parasympathetic
1
What will determine the effects of AChE and NE on effector cells of the autonomic nervous system?
it will depend on effector what happens when it recieves stimulation form ACh and NE
1
What is the sympathetic division of the nervous sustem known as and explain the structure of neurons?
its also known as the thoracolumbar division and all preganglionic fibers come from cells in spinal cord segments T1 to L2--thoracic and upper lumbar region
see other card for structure---how ever the SNS will supply internal organs, sweat glands, arrector pili muscles, and smooth muscle in the walls of all vessels
1
In the SNS, explain the length of the neurons (what is the exception to this rule)
the preganglionic neurons are short while the post ganglionic neurons are long
the exception is chromaffin cells of the adrenal medulla b/c they secrete neurotransmitter directly into circulation
1
What portion of the SNS is branched?
the preganglionic neurons are highly branched and one preganglionic neuron may innervate several organs
1
Explain the structure of the adrenal medulla and the nervous system?
the preganglionic neuron come from the throacic portion of the CNS and synapses on the adrenal medulla---\> it releases ACh---\> the adrenal medulla releases NE and Epi into the blood
1
What is the anatomy of the PSNS and what is another name for it
the PSNS is also known as the craniosacral division because the nerve fibers arise from the cranium (cranial nerves and the sacral portion of the spinal cord
1
Where are the cell bodies of the cranial portion of the parasympathetic system found.
in the midbrain, in the nucleus of the 3rd crainal nerve (oculomotor)-innervate smooth muscles of the eyes: cause pupils to constrict and the lenses to bulge allowing the eye to focus on close objects
in nuclei of the cranial nerve:
- VII (facial)
- IX (glossopharyngeal)
- X (vagus)- account for 90% of preganglionic parasympathetic fibers in the body; it innervates most of the major organs in the thoracic and abdominal cavitie: esophagus, heart, lungs, liver, stomach, spleen, kidney, small intestin, and the promixal halfe of the large intestine
1
Where are the nerves in the sacral portion of the PSNS arise?
sacral area of the spinal cord (S2-S4) and then form the pelvic splanchnic nerve
which innervates the distal half of the large intestine (increases motility), bladder and ureter (causing contraction) and the reproductive organs (causing erection of the penis and clitoris)
1
Explain the overview of view of parasympathetic nervous system ?
found in the brain and sacral portion of the spinal cord
the preganglionic fiber is long w/ minimal branching and the postganglionic fiber is short
the ganglia is within or near the effector organ
1
What is the length of the different nerves of the preganglionic and postganglionic protion of the PSNS?
the preganglionic axons of the PSNS extend from the CNS all the way to the structures they innervate---therefor they are LONG
but the postganglionic cell bodies are very close or even within the target organs and have very short acxons that synapse with effector cells
1
Describe the innervation of the PSNS.
innvervates a more limited portion of the effector organs than SNS
they tend to form a single synapses with postganglionic neurons with the exception of the Auerbach plexus (the gut)
1
Explain the overview of sympathetic nervous system
the site of origin is the thoracolumnar region of spinal cord
the length of fibers: short preganglionic fibers with extensive branching (1:20) and long postganglionic fibers
the ganglia location is close to the spinal cord
1
Give a summary of cholinergic transmission
1. ACoA + choline are combined = ACh
2. ACh is packaged in a vesicle
3. ACh is released
4. ACh binds to receptors on the post-synaptic cell (neuron or neuroeffectors)
5. AChE binds ACh and breaks it down into acetate choline
1
What is aceylcholine, how is it made, and where is it secreted
its a neurotransmitter released by preganglionic neurons of the parasympathetic and sympathetic nercous system
its made from choline + acetyl CoA----\> throug an acetylation reaction with the choline acetyltranferase enzyme to form---\> acetylcholine + coenzyme A
1
How is acetycholine packed into the neuron?
ACh is packaged into synaptic vesicles by a proton dependent vesicular transporter
1
What is the rate limiting step in acetycholine formation and storage into the neuron
the rate-limiting step is choline uptake
choline accumulate into axon terminal by a high affinity Na+ dependent choline transporter
1
What is hemicholinium and what does it do
blocks the high affinity Na= dependent choline transporter that moves choline and Na+ into the axon terminal---to make eventually make ACh
1
What is vesamicol and what does it do
it blocks the proton dependent vesicular transporter that helps package ACh into synaptic vesicles
1
How is acetylcholine released from the neuron (explain detailed steps)
1. transmitter release depends on extracellular Ca2+
2. release occurs when an action potential reaches the termini and triggers Ca2+ influx through voltage dependent Ca2+ channels
3. the synaptic vessels fuse with the presynaptic terminal membrane, resulting in exocytosis of the ACh molecules into the synapse
1
Where are nicotinic receptors?
they are found in both the autonomic nervous system and somatic nervous system
autonomic nervous system: the postganglionic receptors on sympathetc, parasympathetic, and adrenal medulla
somatic nervous system: nicotinc receptors on the skeletal muscle
1
Where are the adrenergic receptors and to what neurotransmitter do they respond?
adrenergic receptors on the effector organs that will respond to (norepinephrine and epinephrine) from the sympathetic postganglionic neurons or the adrenal medulla
1
Where are the muscarinic receptors and to what neurotransmitter do they respond ?
the muscarinic receptors are on effector organs that respond to acetylcholine supplied by the postganglionic neurons from the parasympathetic nervous system
1
What is the enteric nervous system and what does it do?
its an independent nervous system embedded in the wall of the gut--controls gut motility and gut secretion
1
How many neuronal cell bodies does the enteric nervous system contain and what are they composed of ?
contains over 100 million neuronal cell bodies (more than spinal cord)
they are composed to two interconnected plexuses, myenteric and submucosal---poorly understood
1
How does the enteric nervous system receive input?
it gets input from the PSNS and SNS innervation as well as sensory innervation from the intestinal wall
1
Where does motor fibers go in the enteric nervous system?
- motor fibers from the neurons go to the smooth muscle cells
- secretory cells of the mucosa to control motility and secretion
1
How is the enteric nervous system modulated?
its modulated by the autonomic nervous system
so a lesion on PSNS and SNS input but will not stop the activity of the gut
1
What do sensory ending of many enteric neurons secrete?
calcitonin gene-related peptide, cholecystokininm dynorphin, enkephalins, gastrin-releasing peptide, 5-hydroxytryptamine (serotinin), neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide
1
What is non-adrenergic non-cholinergic transmission
widely recognized that autonomic transmission in may organs could not be blocked by drugs that abolish response to NE or Epi
1
How was it determined that there were more transmitters than NE and Epi
fluorescence and immunocytochemical methods
1
What are the most common transmitter substance; but what are the other kinds
peptides are the most common transmitter substance but purines such as ATP are also present; some neurones will contain as many as five different possible transmitters
1
How do the heteroreceptors on cholinergic neurons work
heteroreceptors- alpha-2 sympathetic receptors on a cholinergic neuron
1
How does the receptor modulate the release of neurotransmitters
receptor modulation of the release process can occur by alter ion currents to either hyperpolarize (elevate threshold) or depolarize (decrease threshold) of the axon termina
1
What is another way to modulate synaptic transmission
activation of a second messengar systems -----\> cAMP and cGMP can lead to phosphorylation of various proteins----\> in activity of the axon terminal such as transporters and vesicle proteins
1
Explain the schema of presynaptic autoreceptors
1
What are the two main types of Ach receptors
nicotinic and muscarinic
1
What is the alkaloid muscarine and where does it work; how is the name muscarine receptors fitting
alkaloid muscarine (the poisonous agent in toadstools---Amanita muscaria), have little to no effect on receptors in the autonomic ganglia; mimics ACh on smooth muscle; such as the heart, refered to as muscarinic
1
What are cholinergic receptors
the actions of ACh can be reproduced (or mimicked) by the drug nicotine; actions of ACh in sympathetic ganglia are referred to as nicotinc, and the receptors are termed nicotinic receptors; blocking muscarinic effects followed by larger doses of ACh produce nicotinic effects; along with ganglionic effects, stimulation of voluntary muscle and stimulation of Epi secretion from the adrenal medulla
1
Why is the name nicotinic receptors fitting and how does blocking muscarinic receptors help
1
What are the effects of Ach on nicotinic receptors
nicotinic ACh receptors are ligand gated ion channels that are composed of multiple subunits- arranged as a pentamet with 1-4 distinct subuntis, subunits surround an internal channel
two ACh molecules bind to the receptor and cause the Na+ channel to open to ACh molecules bind to the receptor to cause Na+ channel to open
Na+ then increases within the cell, an action potential is generated leading to a response
1
What type of effects was seen with acetylcholine on the cat''s blood pressure
see page 34
1
What are the two types of cholinergic receptors
muscarinic and nicotinic
1
What are the nicotinic receptors and what is their neutrotrasmitter
Nm found at skeletal muscle and NMJ
and Nn which is the neuronal subtype (ganglia and adrenal gland)
1
How do nicotinic receptors work, describe using the diagram
see page 35
1
What are the two subtypes of nicotinic receptors
Nm and Nn
1
What are muscarinic receptors and what is their neurotransmitter
G-protein coupled receptors that exhibit classical 7 transmemebrane topology: activates second messengers; the neurotransmitter that binds is ACh
1
What are the five muscarinic receptor subtypes
M1-M5
1
How do M1, M3, M5 work (odd numbers)
M1,3, and 5- are coupled to the stimulation of the IP2/DAg pathway via Gq
1
How do M2 and M4 work (even numbers) and what is imporatant about M2 receptors
are coupled to inhibition of cAMP production via an inhibitory G-protein
additionally M2 receptors are coupled to elevation of K+ excretion, which would lead to hyperpolarization, via a G-protein
each subtype has a unique pharmacological profile
1
What is the difference between nicotinic and muscarinic receptors; which is slower and what is this important
speed of action; stimulation of nicotinic receptors produces almost instantaneous responses
1
Summarize the location and function of nicotinic receptors
found in sympathetic and parasympathetic postganglionic neurons at neuromuscular junctions of skeletal muscles, at some cholinergic synapses in the CNS
1
Summarize the location and function of muscarinic receptors
found primarily in the membranes of visceral effectors; for e.g. in the heart, gastrointestinal tranct, arterioles of genitalia, iris of the eye, salivary and sweat glands, lung airways, and urinary bladder
1
Or rare occasion what can Ach interact with what receptors
although the primarily receptors at the ganglia is nicotinic can have M1 receptors
Normally ACh interacts with Nm receptors but on rare occasions can interact with a minor M1 (muscarinic) receptor. The effects of some drugs can be determined based on these receptors.
1
What are the adrenergic receptors
a multitude of subfamilies and subtypes of adrenergic receptors have been identified. Binds Ne, Epi, isoproteranol
1
What is the order of the adrenergic agonist
Aliquist made the first differentiation of subfamilies; He found that the rank order of potency of adrenergic agonists in the stimulation of smooth muuscle contraction in the vasculature was :
epinephrine\> norepinephrine\> isoproteranol
1
What is the rank order of potency for stimulation of heart rate
for the same agonists, the rank order of potency for stimulation of hear rate was
isoproteranol\> epinephrine\> norepinephrine
1
How is the response of the vasculature classified compared to the heart
the response of the vasculature was classified as alpha-receptor mediated while the response in the heart was classified as beta- receptor mediated
1
What molecular tool allowed for classification of alpha and beta receptors
the advent of more selective compounds and the tools of molecular biology have greatly expanded these initial observations; these tools have also allowed for sub-classification of alpha and beta-blockers
1
How do the adrenergic receptors work
all adrenergic receptos are G-protein coupled and therefore activate second messengers they differen in which second messenger they activate, their tissue distribution, DNA sequence and their pharmacological profile
1
How are beta adrenergic receptors classified
currently classified into three subtypes: beta-1, beta-2, beta-3
1
What is the activation of beta-adrenergic receptors coupled to?.
all three subtypes are coupled to the activation of cAMP via Gs
cAMP then activates protein kinase A which can phosphorylate various proteins to either activate or inhibit them
1
Compare the sensitivity of alpha receptors and beta receptors to which neurotransmitter
alpha receptors stimulated mostly by NE
beta receptors more sensitive to epinephrine
1
What is the rule if alpha and beta receptors are both present; give an example
if both are present rule:
alpha= excitation
beta= inhibition
1
What is an exception of the beta and alpha receptor rule
beta-1 receptors stimulate heart to beat faster and stronger; contraction; muscarinic-2 receptos decrease strength of contraction
1
What are types of the alpha adrenergic receptors
two typrd of receptors: alpha-1 and alphaa-2
there are three subtypes of alpha-1: 1A, 1B, and 1D; which are coupled to the activation og IP3/DAG pathay---\> DAG can activate PKC and subsequent protein phosphorylation
IP3 can elevate intracellular ca2+
there are 3 subtypes of alpha-2 receptors: 2A, 2B, and 2D
all are coupled to the inhibition of cAMP stimulation
2A and 2B decreases intracellular ca2+ levels
2A elevates K+ conductance (hyperpolarizing)
1
What are the most common transmitter substance; but what are the other kinds
peptides are the most common transmitter substance but purines such as ATP are also present
1
How do the autoreceptors on adrenergic/cholinergic neurons work
in addition to simulation of post-synaptic receptors neurotransmitters may act upon autoreceptors present on the post synaptic terminal to modulater its own release and uptake process
1
How do heteroreceptors of the cholinergic neuron work?
receptor regulating the synthesis and or the release of mediators other than its own ligand; e.g. alpha-2 receptors found presynaptically on cholinergic neurons activation of NE results in an inhibitior of ACh release
1
What is another way to modulate synaptic transmission
receptor modulation of the release process can occur by altering ion currents to either hyperpolarize (elevate threshold) or depolarization (decrease threshold) of the axon terminal
Alternatively, activation second messenger systems such as cAMP or cGMP can lead to phosphorylation of various proteins involved in the activity of various proteins involved in the activity of the acon terminal such as transports and vesicle proteins
1
What are the two types of cholinergic receptors
muscarinic and nicotinic receptors
2
After the Ach is released what happens next
it will diffuse across the synapse where it binds to and activates the cholinergic receptors
3
What is aceylcholinesterase and what does it do
it terminates the actions of ACh its located in the postsynaptic cell membrane
4
How is acetylcholine broken down and how fast does this happen
acetylcholine breakdown by acetylcholinesterase in less than one millisec
5
Why is it impoartant that acetylecholine be broken down
its important in skeletal muscle to prevent diffusion anc activation of neighboring receptors
6
What are the by products of acetylcholine hydrolysis and what happens to the products
they are choline and acetate and both are reused in the ACh synthesis
7
Summarize adrenergic transmission
1. the presynaptic cell (which is the post ganglionic fiber)
MAO and COMT enzymes package the neurotransmitters
2. The neurotransmitters NE, Epi, and dopamine are released
3. land on muscarinic post-synaptic cells with receptors
4. if there is alot of NE, Epi, or dopamine they can work back on the receptor A2 and inhibit MAO and COMT
5. There is also a re-uptake transporter to lower the amount of neurotransmitters
8
How is dopamine, NE, and Epi made
all of these are made from tyrosine
9
What are catecholamines
dopamine, NE, and Epi
10
What is the rate limiting enzyme in the formation of catecholamines
tyrosine hydroxlase
11
where is epi produced and where is it not produced
epi is produced in the chromaffin cells of the adrenal medulla but not in the sympathetic neurons
12
What is important to remember about the enzymes involved in catecholamine synthesis
they are not completely specific
for example, serotonin can be made by dopa decarboxylase using L-trytophan
13
Explain the steps of catecholamine synthesis
1. tyrosine w/ enzyme tyrosine hydrolyase: Dopa
2. Dopa w/ enzyme dopa decarboxylase: Dopamine
3. Dopamine w/ enzyme Dopamine beta hydroxylase: norepinephrine
4. Norepinephrine w/ enzyme phenylehanolamine- N- methyltransferase: epinephrine
14
Explain the steps of catecholamine synthesis relative to the neuron
1. tyrosine is taken into the neuron by an amino acid transporter
2. Dopamine is made in the cytoplasm and is transported into vesicles by a proton dependent non-selective monoamine transporter with ATP
Feed back includes:
1. adrenergic receptors can activate tyrosine hydroxylase by phosphorylation
2. the rate of Epi synthesis can be regulated by glucocorticoid levels, which induce synthesis of PMVT (phenylethanolamine-N-methyltransferase)
15
How are catecholamines released
1. axon terminals become depolarized
2. voltage sensitive Ca2+ channels open
3. synaptic vesicles move toward and fuse with presynaptic membrane
4. NE released into synapse with ATP, DBH, and peptide cotransmitters
5. NE travels across synapse and binds to a wide variety of adrenergic receptors
16
What is the difference between Epi release and NE release
Epi is released into blood circulation always
17
What can inhibit NE release
bretylium and guanethidine
18
How are the effects of NE and Epi terminated
uptake of these neurotransmitters into the presynaptic terminal or diffusion to other uptake sites such as glia cells stops their effects
19
How can the NE transporter be blocked
NE transport is Na+ dependent and can be blocked by certain drugs
20
What does the transporter have greater affinity for?
the Na+ dependent uptake transporter has greater affinity for NE
