Autonomic Nervous System Flashcards
Somatic nervous system (SNS) pathway
sensory part of PNS = skin, muscle input (afferent) CNS output (efferent) motor part of PNS = voluntary SNS effectors = skeletal muscle
Visceral nerves (organs) pathway
sensory part of PNS afferent CNS efferent motor part of PNS = ANS - involuntary effectors = smooth muscle, cardiac muscle, glands
Fight or flight
sympathetic
exercise, embarrassment
whole body response or discrete and organ specific (reproductive system)
heart rate inc, eyes dilate, lungs inc in vol, liver breaks down glucose to get in bloodstream
Rest and digest
parasympathetic
digestion, defaction, diuresis
funcitons in discrete, organ specific manner
heart rate dec, eyes constrict, GI tract and glands stimulated for digestion
dual control (and exceptions)
one starts = other stops
generally innervate same tissues but have opposite effects
actions are antagonisitic but work synergistically
allows rapid, precise control of tissue function
exceptions, sympathetic innervation only:
sweat glands, hair follicles, blood vessel smooth muscle, adrenal medulla
Ganglion
neuronal cell bodies outside of CNS
pre gang - post gang - target cell = in both sympathetic and parasympathetic but not in adrenal medulla
Preganglionic neurons
always cholinergic fibres e.g. release ACh as primary neurotransmitter
ACh activates nicotinic ACh receptors on post synaptic cell
Sympatheic pathway
short, cholinergic pre gang neurons from thoracic and lumbar spinal cord
long, adrenergic post gang neurons
target tissue expresses alpha and beta agrenergic receptor
Adrenal medulla
chromaffin cells function similar to post gang neurons but release mainly adrenaline (epinephrine)
target tissues express alpha and beta adrenergic receptors
Parasympathetic system
long, cholinergic pre gang neurons from brainstem and sacral spinal cord
short, cholinergic post gang neurons
target tissues express muscarinic ACh receptors
Importance of vagus nerve
carries 80% of parasympathetic outflow
also carries lots of visceral afferents - vagal nerve stimulation
essential components of ANS
spinal cord (in later horn)
- mediates autonomic reflexes
- receives sensory afferent and brainstem input
brainstem nuclei
- mediate autonomic reflexes
regulation of ANS output
forebrain
- minimal concious cortical control but cortical processes do regulate auto output e.g. anxiety and stress can lead to GI disturbances
visceral afferents
- sensory input from them takes priority over cortical function e.g. bladder distension
principle transmitters in ANS
- act upon …
ACh
Noreadrenaline
- nAChR, mAChR and alpha and beta adrenoreceptors
all pre gang neurons use …
it acts upon …. post gang
- ACh
acts upon nicotinic post gang
in sympathetic NS, most organs innervated by post gang sympathetic neurons use… ( + exception)
in parasympathetic NS, all post gang neurons use …
NA
exception = sweat glands - use ACh
Ach on muscarininc receptors
ACh receptors - 2 types
- …. actions closely resemble ….
antagonists of receptors
muscarininc = organs, PNS
nicotinic = pre –> post ganglionic
2 types of activity seen by ACh, one mimicked by muscarine and the other nicotine.
muscarininc actions closely resemble effects of parasymp innveration
muscarinic = atropine
nicotinic = curare
what happens if muscarininc effects have been blocked by atropine?
larger doses of ACh produce nicotinic-like effects:
stimulation of all autonomic ganglia, voluntary muscle and secretion of adrenaline from adrenal medulla
types of muscarininc receptors
= GPCR
- M1,3,5 = coupled Gq proteins = inc PLC, inc IP3 and intracell Ca
- M2,4 = coupled Gi proteins = dec adenyl cyclase, dec cAMP, inc GIRK, dec voltage gated Ca channels
M1 receptor
- where
- function
- autonomic ganglia, common on post synaptic mAChR , smooth muscle and gland cells
- stimulate contraction of smooth muscle = inc bronchoconstriction, inc GI mobility and emptying of bladder
M2 receptor
- where
- function
- abundant in nodal and atrial tissue, sparce in ventricles
- M2 agonists activate GIRK channels and inhibit L-type Ca channels
- receptors are negatively coupled to adenyl cyclase via Gi = dec cAMP = inhibits opening of L-type Ca channels and reduce Ca current
- also open GIRK channels via beta-gamma subunits = inc K permeability = hyperpolarisation that opposes inward pacemaker current, slowing heart and dec automaticity
- mediate effects of pilocarpine and slow down heart rate: open GIRK by b-g binding to channel - hyperpolarising pacemaker = slow action potential firing
M3 receptors
- where
- function
- exocrine glands, smooth muscle, blood vessels
- regulates production of NO - vasodilation and drop in blood pressure
- inc mucus in lungs, stimulate lacrimal glands (tears), sweat and salivary glands
M4 and M5 receptors
- location
- function
M4 = CNS = enhanced locomotion M5 = CNS - very localised expression, salivary glands = unknown
Muscarine
cholinergic agonist at mAChR
from mushroom, less than 1g can cause nausea
dependant on dosage:
dec blood pressure (due to action on endothelial cells)
inc saliva, tears, sweating
abdo pain
death from cardiac failure (slow heart rate) and respiratory failure
Clinical uses of muscarine?
due to lack of selective agonists = limited
- Cevimeline = M3 selective = used to improve salivary and lacrimal secretions in Sjögren’s syndrome - autoimmune diesease which causes dry eyes and mouth
- Pilocarpine eye drops = treat glaucoma, reduces pressure in eye by increasing drainage into bloodstream
note: any drug used must not cross blood-brain barrier into CNS
Atropine
muscarinic agonist
non selective - works on all 5 receptors
inhibits saliva, lacrimal, bronchial and sweat secretions
smooth muscle relaxant = bronchial, biliary, urinary tract
pupil dilation
modest inc in heart rate
dec GI motility, acid secretion
CNS - agitation and disorientation
inc body temp
- Pirenzipine = M1 selective = controls acid secretion into gut for peptic ulcer treatment
- Darifenacin = M3 selective = relaxes smooth muscle for overactive bladder
indirect enhancing drugs
cholinomimetic = mimick effect of activating cholinergic signalling pathways
inhibition of cholinesterase = found is CSF, synaptic cleft at cholinergic synapses and merve terminals, inhibit enzyme = indirectly inc ACh
Anti - cholinesterase drugs
- physostigmine = used topically for glaucoma
- nerve gas (serin), organophosphates, pesticides = long acting (irreversible), leads to signifcant build up of ACh and inc activation of musc and nic receptors
note: if they enter brain they effect ALL cholinergic transmission = dangerous
Noradrenaline receptors
GPCRs
found on tissues responding to post ganglionic neurons
NA acts on alpha and beta adrenergic receptors
B2 selective agonists = treta asthma as they cause bronchi to relax but B1 effects must be avoided as they increase contractility of the heart and can cuase cardiovascular issues
NA receptor subtypes = charaterised by signalling molecule and pharmacology
a1 a2 B1 B2 B3
alpha 1 adrenoreceptor
- G protein coupling
- 2nd messenger
- selective agonists
- selective antagonists
- Gq
- PLC activation, inc IP3, inc Ca
- phenylephrine
- prazosin
alpha 2 adrenoreceptor
- G protein coupling
- 2nd messenger
- selective agonists
- selective antagonists
- Gi/Go
- dec cAMP, dec Ca channels, inc K channels
- clonidine
- idazoxan
B1 adrenoreceptor
- G protein coupling
- 2nd messenger
- selective agonists
- selective antagonists
- Gs
- inc cAMP
- dobutamine
- atenolol
B2 adrenoreceptor
- G protein coupling
- 2nd messenger
- selective agonists
- selective antagonists
- Gs
- inc cAMP
- salbutamol - B2 in lungs = bronchodilation
- butoxamine
B3 adrenoreceptor
- G protein coupling
- 2nd messenger
- selective agonists
- selective antagonists
- Gs
- inc cAMP
- mirabegron
- N/A
Receptor signalling in heart
via Gs
- voltage gated Ca channel activated joined by activated PKA = phosphorylation leads to increased open time of channels = more NA can enter = inc Ca in cardiac muscle cells = inc contraction
Clinical uses of adrenoreceptors
- agonists
adrenaline = non selective, cardiovascular system, used for cardiac arrest and anaphylaxis
salbutamol = B2 selective, respiratory system, bronchodilator
nasal decongestants = ephedrine - works by indriectly stimulating NA release, cause constriction of smooth muscle in nose vessels
Amphetamines
indirectly acting sympatomimetic drugs (recreate increased signalling via NA)
structurally related to NA, doesnt act directly on receptors but indirectly by increasing release of endogenous NA
‘false substrates’ taken up by transporters in NA receptors, amphetamine gets stuck in cell whilst moving NA out of cytosol
Clinical uses of adrenoreceptors
- antagonists
prazosin - a1 selective = hypertension carvedilol - a and b = heart failure porpanalol - B1 and 2 = anxiety - unwanted effects: bronchoconstriction - beta blockers avoided in asthma patients cardiac depression - elderly bradycardia fatigue cold extremities
