Introduction to ANS Flashcards
Autonomic Nervous System
• AUTONOMOUS • NOT UNDER DIRECT CONSCIOUS CONTROL • VISCERAL FUNCTIONS • CARDIAC OUTPUT, BLOOD FLOW TO VARIOUS ORGANS, AND DIGESTION • Common with endocrine system • Extensive use of negative feedback • Chemicals for neurotransmission between nerve cells and effector cells • From nerve terminals to synaptic cleft thru diffusion and postsynaptic cell through receptors
. Characteristics of Autonomic Nervous System, except A.Direct control B.Autonomous C.Necessary for life D.Can influence cancer development and progression
Direct Control
TWO MAJOR DIVISIONS
SYMPATHETIC: THORACOLUMBAR PARASYMPATHETIC: CRANIOSACRAL • BOTH ORIGINATE IN NUCLEI WITHIN THE CENTRALNERVOUS SYSTEM • Preganglionic efferent fibers that exit from the brain or spinal cord, terminate in motor ganglia
Sympathetic preganglionic fibers leave CNS through thoracic and sacral spinal nerves A.True B.Maybe C.False D.I need to go back to First Year
False- Thoracolumbar
PARASYMPATHETIC PREGANGLIONIC FIBERS LEAVES CNS THROUGH
CN 7,7,9,10, S3 and S4
Parasympathetic preganglionic fibers are short and located in the prevertebral ganglia A.True B.Maybe C.False D.I need to go back to First Year
True
Preganglionic fibers (short)
terminate in ganglia located in
paravertebral chains
preganglionic fibers (long)
prevertebral ganglia
Postganglionic fibers
from the ganglia run to tissues innervated
Some Preganglionic fibers: terminate in
parasympathetic ganglia located outside the
organ innervated
- CILIARY
- PTERYGOPALATINE
- SUBMANDIBULAR
- OTIC
- SEVERAL PELVIC GANGLIA
Enteric Nervous System
• Located in the walls of the GIT • Includes: Myenteric plexus (Auerbach) Submucous plexus (Meissner) • Receives: • preganglionic fibers (parasympathetic) • Postganglionic fibers (sympathetic) • Sensory input from gut walls
Ratio of Preganglionic to post ganglionic
Sympa: 1:20
para: 1:1 to 1:3
ACTIVITY of SYmpa and Para
Symp: Dischrge of system
para: Discrete organs
Neuro Eff Junctions PSNS and SNS
SNS- diffuse branching
PSNS- Concentrated in one region
Som NS- Discrete, organised, Ach Recep located on the motor end plate
Neurotransmitter and receptor type in Ganglion
SNS- ACh/nicotonic recep
PSNS- ACh/nicotinic
Neurotransmitter in Eff. organs
SNS: Norepi
PSNS and Som: ACh
Receptor types in eff, organs
a1, a2, b1, b2- SNS
PSNS- M
Som: Nic
Mammalian neuromuscular junctions
relatively “tight” and closely innervated to
facilitate rapid and very short effects
Autonomic junctions terminal and effector cells
smooth muscle, cardiac muscle and glands
are released from a chain of varicosities in the
postganglionic fibers in the region of the
smooth muscle; wider than somatic clefts.
Hence, effect is slower and may inhibit or
activate many effector cells
ACETYLCHOLINE
CHOLINERGIC
NOREPINEPHRINE
ADRENERGIC
Steps Involved in
Neurotransmission
Synthesis
Storage
Synthesis
Cholinergic transmission: Acetyl CoA
(mitochondria) and choline (ECF by CHT)
Enzyme: CHOLINE ACETYLTRANSFERASE (ChaT)
Adrenergic transmission: Tyrosine is transported into noradrenergic ending Sodium dependent
carrier
Storage
Cholinergic: Transported into the
vesicle Vesicle Associated
Transporter (VAT) Vesicles V-SNARE and T-snare
Adrenergic: Tyrosine is converted to dopamine Transported into the vesicle VMAT (vesicular monoamine
transporter) Conversion of tyrosine to dopamine
Synthesis Blocked by
Cholinergic: hemicholinium
Adrenergic: Met tyrosine
Storage blocked by
Choli: Vesamiciol
Adre: Reserpine
Release of neurotransmitter
Choli: Calcium interacts with VAMP, Exocytotic expulsion
Adre: Dopamine converted to Norepi
Dopamine- b-hydroxylase
Dopamine is released by diffusion
Termination of
activity
Choliner: Acetychylcholine
esterase Splits acetylcholine
into acetate and choline
Adre: NET : norepinephrine transporter Carry transmitter back to the vesicle DAT/SERT: reuptake of serotonin and dopamine Termination of activity Simple diffusion Reuptake by NET
Release
Choli: Blocked by
Botulinum toxin
Tetanus toxin
(CNS)
Adre: Tyramine, Amphetamines and
Ephedrine (agonist)
Bretylium and Guanethedine
Termination of
activity
Choli: Blocked by
Cholinesterase
Inhibitors like
Neostigmine
Adre: Inhibit reuptake by Cocaine and certain antidepressant drugs Tranylcypromine, phenelzine, rasagiline, selegiline (MAO inhibitor) Increase MAO in the CNS
Storage and release of transmitter
- Modulation of Transmitter release
Interaction of the transmitter with postjunctional
receptors and production of the postjunctional
potential
Transmitter diffused across the synaptic or junctional cleft and combines with specialized receptors (superfamily of ionotrophic receptors) on the postjunctional membrane, often resulting in a localized increase in ionic permeability or conductance of the membrane. 5HT3 Purine
receptors, GABA acid and Glycine receptors are examples
Presynaptic Receptors
Hetero and Auto
Heteroreceptors
Respond to neurotransmitters,
neuromodulators or neurohormones
released from adjacent neurons or cells
•NE can influence the release of Ach from parasympathetic neurons by acting on A2, A2b, and A2c receptors •Ach can influence the release of NE from sympathetic neurons by acting on M2 and Me receptors
Autoreceptors
Located on or close to axon terminals of a neuron through which the neuron’s own transmitter can modify the transmitter synthesis and release Examples: •NE released from sympathetic neurons may interact with A2a and A2c receptors to inhibit neurally released NE •Ach released from parasympathetic neurons may interact with M2 and M4 receptors to inhibit neurally released Ach
Initiation of postjunctional activity
if an EPSP exceeds a certain threshold value, it imitates a propagated action potential in a postsynaptic neuron or a muscle action potential in
skeletal or cardiac muscle by activating voltage sensitive channels in the immediate vicinity
Nonelectrogenic functions
trophic actions/ factors of neurotransmitter either synthesis or
inactivation of transmitter, receptors, and synaptic characteristics
Acetylcholine
Primary transmitter at ANS ganglia, at somatic neuromuscular junction, At parasympathetic postganglionic nerve endings Excitatory transmitter to smooth muscle and secretory cells (ENS) Major neuron to neuron transmitter (ENS)
Norepinephrine
Primary transmitter at most sympathetic
post ganglionic nerve endings
Adenosine
triphosphate
Transmitter or co-transmitter at many
ANS effector synapse
Calcitonin gene
related peptide
In Substance P in cardiovascular
sensory nerve fibers, secretomotor
ENS, a cardiac stimulant
Cholecystokinin
Cotransmitter in some excitatory
neuromuscular ENS
Dopamine
Modulatory transmitter in some
ganglia(ENS), a postganglionic
sympathetic transmitter in renal blood
cells
Enkephalin
Secretomotor and interneurons (ENS)
Inhibit acetylcholine release and
inhibit peristalsis, stimulate secretion
Galanin
Secretomotor neurons, apetite
satiety mechanism
GABA
Presynaptic effect on excitatory ENS
nerve terminals, relaxant effect on
the gut, not a major transmitter
Nitric oxide
Cotransmitter at inhibitory
ENSneuromuscular junction,
important in sphincters
Gastrin
releasing
peptide
Potent excitatory transmitter to
gastrin cells. Mammalian bombesin
Neuropeptide Y
In noradrenergic neuron, some secretomotor neurons (ENS) Inhibit secretion of water and electrolytes in the gut Long lasting vasoconstriction Cotransmitter(parasympathetic)
Serotonin
Important transmitter or cotransmitter
at excitatory neuron to neuron
junctions (ENS)
Substance P
Impt. Sensory neuron transmitter in
the ENS, excitatory cotransmitter with
ACH, vasodilator
Two main families of acetylcholine
receptors
Muscarnic (G protein)
Nicotinic- (Ligand gated)
both Presynap and post synap
Location of Neuron cell bodies
SPre GN :Intermediolateral cell in Spinal cord (T1-L3)
SPostGN: Prevertebral and paravertebral
ParaPreGN: Brainstem and scaral
ParaPostGN: Terminal ganglia in or near target organ
Myelination
SPreGn and ParaPreGn: yes
SpostGN, ParaPostGN: No
Primary neurotrans
SpreGn, ParaSympPGN and PAraPostGN: ACh
SpostGN: Norepi
Primary post synaptic Receptor
SpreGn and ParaPre: Nicotinic
SPost- Adrenergic
Parapost: Muscarnic
Muscarinic receptors
Bind both acetylcholine and muscarine
Cholinergic transmission (acetylcholinemediated) activates muscarinic receptors autonomic ganglia, organs innervated by the parasympathetic division of the autonomic nervous system and in the central nervous system
All muscarinic receptors are Gprotein coupled receptors
five subclasses of muscarinic
receptors
M1 (CNS), M2 (Heart), M3 (Smooth muscle), M4 (CNS), M5(CNS)
M1,3,5- Excitatory
M2,4- Inhibitory
Nicotinic receptors
Nicotinic receptors are ligand-gated ion
channels
When bound to acetylcholine
receptors undergo a conformational change
allows the entry of sodium ions
result in the depolarization of the effector
cell.
N1 or NM receptors
acetylcholine receptors at
the neuromuscular
junction
•NM subtype
are the only
acetylcholine receptors that
can be found at the
neuromuscular junction.
N2 or NN receptors
transmission of cholinergic signals in the autonomic nervous systems Nicotinic receptors
NN subtype
can be found both at cholinergic and adrenergic ganglia, but not at the target tissues (e.g, heart, bladder, etc) •Receptors are also present in the CNS and adrenal medulla.
M1 Post receptor Mechanism
IP3. DAG cascade
M2 Post receptor Mechanism
inhibition of adenyl cyclase
M3 Post receptor Mechanism
IP3, DAG cascae
M4 Post receptor Mechanism
inhibition of Adenylyl Cyclase
M5 Post receptor Mechanism
`
IP3, DAG cas, IC Ca+2
Nm and Nn Post receptor Mechanism
Na/K depol
M1
CNS neuron, sympathetic postganglionic,
some presynaptic
M2
Myocardium, smooth muscle, presymaptic
site, CNS neurons
M3
Exocrine gland, vessels, CNSneuron
M4`
CNS neuron, vagal nerve endings
M5
Vascular endothelium, cerebral vessels,
CNS neurons
Nm
Postganglionic neurons, presynatic
cholinergic
Nn
Skeletal muscle neuromuscular endplates
Adrenergic (noradrenergic)
receptors
Are class of G protein-coupled receptors
that are targets of many
catecholamines like
norepinephrine (noradrenaline) and
epinephrine (adrenaline) produced by the
body, but also many medications like beta
blockers, beta-2 (β2) agonists and alpha-2
(α2) agonists, which are used to treat high
blood pressure and asthma, for example.
EPI > NE»_space; Isoprotenerol
Alpha receptors
Isoprotenerol > EPI > NE
Beta Receptors
Alpha 1 Post receptor Mechanism
IP3 and DAG.\Ca+2
Alpha 2 Post receptor Mechanism
Inhibit adenylyl cyclase, Decreased cAMP
Beta 1, B2, B3
Stim. Adenylyl cyclase, inc. cAMP
Alpha 1
Postsynaptic effector cells, smooth
muscle
Alpha 2
Presynaptic adrenergic, platelets,
lipocytes, smooth muscle
Beta 1
Postsynaptic effector cells, heart, lipocytes, brain, presynaptic adrenergic and cholinergic nerve terminals, JG apparatus, ciliary body epithelium
Beta 2
Postsynaptic effector cells, smooth
muscle and cardiac muscle
Beta 3
Postsynaptic effector cells, especially
lipocytes, heart
D1
Stim. Adenylyl cyclase, inc. cAMP
Brain, effector tissue, smooth
muscle of renal vascular bed
D2
Inhibition of adenylyl cyclase, activation of K channels Brain, effector tissue, smooth muscle; presynaptic nerve terminal
D3
Inhibition of adenylyl cyclase
Brain
D4
Inhibition of adenylyl cyclase
Brain, cardiovascular system
: iris(radial M) SNS
iris(circular M)
Contracts, Alpha 1
Ciliary muscle SNS
Relaxes, Beta 1
SA node SNS
Accelerates, B1,2
Ectopic pacemaker SNS
Accelerates B1,2
Contractility SNS
Increases,, B1,2
Bronchiolar smooth SNS
muscle
Relaxes beta2
Smooth muscle
wall SNS
Relaxes Alpha2, beta2
Sphincter SNS
Contracts
Alpha 1
Bladder wall
SNS
Relaxes
Sphincter SNS
Contracts Alpha 1
Uterus, pregnant SNS
Relaxes Beta 2
Contracts Alpha
Penis, seminal vescicle SNS
Ejaculation, Alpha
pilomotor smooth
muscle SNS
Contracts, Alpha
Sweat glands, thermoregulatory
apocrine (stress)
SNS
Increases, m
Increases alpha
Liver SNS
Gluconeogenesis Beta2, alpha
Glycogenolysis, Beta2,alpha
Fat cells SNS
Lipolysis B3
kidney SNS
Renin release, B1
iris(radial M)
iris(circular M) PNS
Contracts, M3
Ciliary muscle
Contracts, M3
SA node
Deccelerates, M2
Ectopic pacemaker
Contractility
Decreases, M2
Skeletal muscle vessel
endothelium
Releases EDRF, M3, M5
Bronchiolar smooth
muscle
Contracts M3
Smooth muscle
wall
Contracts, M3
sphincters
Relaxes M3
Secretion of git
Increases M3
Bladder wall
Contracts M3
Sphincter
Relax, M3
uterus Preg
Contract, M3
penis, Sem V
Erection, M
No effects
Skin, and metabolism
EYE
Iris radial muscle
Iris Circular muscle
Ciliary muscle
Mydriasis (A1)
No effect
Relaxes (Beta)
No effect
Miosis (M3)
Contraction (M3)
SA node
Contractility
Tachycardia (B1>B2)
Increase (B1>B2)
Bradycardia (M2)
Decrease (Atria) (M2)
Skin, Splanchnic
Skeletal M vessels
Endothelium vessels of
Heart, Brain & Viscera
Constrict (A1>A2) Dilation (B2, less M3) No effect No effect Synthesize and release EDRF (M3,M5)
Bronchial Smooth
Dilation (B2)
Constrict (M3)
Smooth muscle walls
Relax (A2, B2)
Contract (M3)
Smooth muscle
sphincters
Contract (A1)
Relax (M3)
Secretion
Increase (M3)
(para)
Bladder wall (detrusor)
Relax (B2), Contract (M3)
Trigone and bladder
sphincter
Contract (A1)
Relax (M3)
Uterus, pregnant
Relax (B2) Contract (M3) no
sensitive
Penis, Seminal Vesicle
Ejaculation (A) Erection (M)
Sweat, Salivary,
Lacrimal,
Nasopharyngeal
Para M, increase, no Symp
Pilomotor smooth
muscle
Contracts (A), no PAra
Eccrine sweat glands
Increase (M)
Its sympathetic but Ach
Mediated no Para
Apocrine (stress sweat
glands)
Increase (A)
No para
Liver, no para
Gluconeogenesis (B2, A)
Glycogenolysis (B2, A)
Fat cells no Para
B3, lipolysys
Kidney
Renin release (B1); No effect
Autonomic Drugs
Sympathetic, Sympathomimetic, sympatholytic
parsympa Drugs
Parasympathomimetic
Parasympatholytic
Muscarnic Agents
Musc ACh receptor, inc. parasympa, ACh, Pilocarpine, Glaucoma (open Aq humor)
Bethanechol- Difficulty urinating
ACh Inhibitors
No recpetor, Indirect efffect on ACh receptors, Prolong
Neostigime: Myasthenia Gravis
Sarin- Chemical warfare
Sympathomimetics
Adregenric receptors, Increase sympa activity, Albuterol, Asthma
Phenylephrine- Cold
Sympatholytic
Adregenic receptors, Dec. Sympa activity, propanolol, hypertension cure
Primary controlled variable in CV
- Mean arterial pressure
- Drug induced leads to increased PVR
- Homeostatic secondary response
Drug effect: Norepinephrine
- Slow infusion on the heart: direct effect
- vasoconstriction
- Increase peripheral vascular resistance
- Increase mean arterial pressure
Intact reflexes
negative feedback baroreceptor response •Increased mean arterial pressure •Decrease sympathetic outflow •Increase parasympathetic effect
Bradycardia
reflex
compensatory response
•PARASYMPATHETIC:
TROPHOTROPIC
•Rest and digest
•Example: slowing of the heart,
stimulation of digestive activity
SYMPATHETIC:
ERGOTROPIC
•Fight or flight
•Example: cardiac stimulation, increased
blood sugar, cutaneous vasoconstriction
Dilation of the radial muscle of the iris with alpha adrenoceptor agents leads to decrease in intraocular pressure in patients with angle-closure glaucoma
True
Nerve terminals carrying regulatory receptors that maybe activated by substances released from other nerve terminals A.Autoreceptors B.Heteroreceptors C.V-AMP receptors D.ABC Transporters
ABC
Effect of receptor regulation that occurs in denervation supersensitivity A.Up-regulation B.Down-regulation C.Modulation by other simultaneous events D.None of the answers
up reg
Type of receptor that activates
the first IPSP in autonomic ganglion
cell
Nicotinic