The main physiological effects of parasympathetic nervous system.
Pupil: constricts Saliva and tear production: stimulates Bronchi: constricts Heart: slows Stomach,pancreas and intestines; stimulates Urination: stimulates Genitals: promotes erection
Effects on the heart
- Stimulation of the Parasympathetic nerve to the heart which is the vagus nerve results in decreased force of contraction reducing heart rate
Cardiac effects - vagus - SAN and atria - Vagus limited distribution than cardiac accelerator nerve which are the sympathetic
nerves coming to the heart - Found innervating sinoatrial node , atrioventricular node and atria - there are not too
much parasympathetic influence in the ventricles - Vagal stimulation - the height of action potential ( how depolarized it gets ) reduces
largely - The resting membrane potential becomes more negative - it hyperpolarizes
- Rapid reduction in frequency of contraction - the heart rate decreases
Effects on blood vessels
Acetylcholine produces considerable vasodilatation to systemic arteries - this is if acetylcholine can get to the artery - we said if because acetylcholine is broken down very easily by choline esterase
- There is far less parasympathetic innervation in arteries compared to sympathetic
Effects on male genitalia
One arterial bed with rich parasympathetic innervations = penis
- Stimulation of parasympathetic nerve going to the penis results in dilation of penile artery and the filling of the corpus cavernosum with blood and the impingement of
the outflow vein all of these things increase the amount of blood within the penis resulting in the physiological effect
Effects on non vascular smooth muscle
Parasympathetic nerve have considerable physiological role to produce contraction
- Stimulating parasympathetic nerve will cause the contraction of bladder detrusor -
smooth muscle found in the wall of the bladder. The detrusor muscle remains relaxed
to allow the bladder to store urine, and contracts during urination to release urine.
- Stimulating the parasympathetic nerve will cause urine to flow out if the urethra is
open
- Parasympathetic nerves going to airways - acetylcholine released from these nerves
produce bronchoconstriction
- There is a longitudinal layer and circular layer of smooth muscle in gastrointestinal
tract acetylcholine will produce contraction of these muscles
- In Terms of non vascular smooth muscle ( bladder airway and GI tracts ) you get
acetylcholine mediated contraction
Eye
Acetylcholine also leads to contraction of circular muscle in the eye
- Parasympathetic nerve leads to contraction of circular muscle leading to narrowing of
the pupil
Eye accommodation
- Parasympathetic nerves release acetylcholine onto the ciliary muscle leading to
bulging of the lens and accommodation to focus on near structures
The ciliary muscle by constricting the suspensory ligaments becomes more relaxed,
allowing the lens to bulge. Therefore light coming from close structure will be focused
onto the retina
- Visual reflex for focusing in something near is to narrow the pupil cutting external
peripheral light
- The lens bulges to focus light rays
Various secretions
Parasympathetic nerve have effect in prompting sections including
- Saliva , gut acid- where is has direct effect on the parietal cells that make the acid as
well as enterochromaffin cell that produce histamine which then stimulates the parietal cells so it has double effect , tears , acetylcholine also increases sweating - this is a sympathetic effect
This farmer has overused the insecticide parathion. What happens next?
- Cholinesterase breaks down acetylcholine. But parathion acts as an inhibitor
preventing the enzyme from doing its job so there will be a buildup of acetylcholine
- The physiological effect - he will have increased bowel motility and increased acid
secretion
- Increased salivation
Cholinergic neurons
Choline is taken up via sodium choline transporter ( symporter )
- Choline combine with acetyl co enzyme a results in production of acetylcholine via
enzyme choline acetyltransferase
- Acetylcholine packaged into vesicles
- Influx of calcium following activation and depolarization of the nerve terminal brings in
calcium
- Causes snare proteins to interact pulling vesicle towards membrane where they fuse
allowing vesicle to release its content
- Acetylcholine will then interact with receptors
- ALWAYS REMEMBER ACTION OF ACETYLCHOLINE IS KEPT BRIEF BECAUSE
OF CHOLINE ESTERASE THAT BREAKS DOWN AC
There are compounds that inhibit activity of cholinesterase including:
- Neostigmine
- Physostigmine
- Edrophonium
- Parathion ( insecticide )
- The inhibition of cholinesterase leads to a build up of AC \
Chemical and receptors involved in the parasympathetic responses
- 2 families of cholinoreceptors - nicotinic and muscarinic - these meditate the parasympathetic response
N1 or NM- skeletal muscle
N2 or NN- autonomic ganglia CNS
M1 CNS, peripheral neurons, parietal cells
M2 atria, SAN, AVN
M3 Visceral smooth muscle, secretory glands, endothelial cells
M4 and M5 for CNS
Nicotinic selective agonist: nicotine, labeline
- Selective antagonist: tubocararine, hexamethonium, Pancuronium
- Muscracinic slestive againits: muscarine, bethanecol, pilocarpine
- Selective antagonist : Atropine ( blocks all muscarinic receptors ) , hyoscine
Pirenzepine, Ipratropium
NICOTINIC acetylcholine receptors
The influx of calcium ion upon its activation produces an excitatory junction potential in the target cell - target cell either in CNS, postganglionic fibre of autonomic nervous system or skeletal muscle
- M1 ,3 and 5 - odd ones - they are positively coupled to phospholipase c
- M2 and 4 - negatively coupled to adenylate cyclase - [cAMP] goes down
- Mainly all the effects mentioned above are mediated by acetylcholine working on
M2and M3 receptors
Activation of M2 receptors in sinoatrial node and atria
- Acetylcholine released from vagal nerves activating the receptor, Effect = slowed heart rate and reduced force of contraction
How does this work?
- - M2 is negatively coupled to adenylate cyclase meaning it is reducing cAMP conc
meaning less activation of pacemaker conductance in the heart so pacemaker is
less active resulting in slower heart rate - Less protein kinase a is being activated so calcium channels are reduced - less
sensitive to membrane voltage - The release of calcium from the SR (sarcoplasmic reticulum) is less effective
- All of this will work to bring down the force of contraction as well as the rate of
contraction - Beta gamma subunits also have functional role in the heart where they activate a potassium channel - which causes the membrane potential to hyperpolarize limiting activation
Activation of M3 receptors contracts non vascular smooth muscle
particularly : - GI tracts - Bladder - Airways - Uterus - Iris How does this work?
- For smooth muscles to contract there has to be increase calcium ions which binds to myosin light chain kinase turning on myosin which at rest is not structurally strong the MLCK phsorpyklates the mysoin now it is structurally strong
Where does the calcium come from to contract the muscles - M3 receptors are coupled to gq/11 these when activated turn on phospholipase c
- The substrate for PLC = PIP2 this is cleaved resulting in diacylglycerol and IP3
- IP3 diffuses to internal calcium store releasing calcium stimulating MLCK leading to
contraction
Activation of M3 receptors indirectly relax arteries
- In blood vessels you have thin monolayer known as endothelial
- The muscarinic receptors are not on the smooth muscle but are heavily expressed in
the endothelial - Here you don’t get contraction because there are no contractile proteins - what it
does is turn on enzyme called NO synthase ( NO= nitric oxide ) - NO synthase makes nitric oxide the starting material = arginine which is converted to
NO - This diffuses to our smooth muscle making it relax
- If Ach is able to stay long enough (when you block cholinesterase) it will stimulate
endothelial located m3 receptors and instead of getting contraction you get NO mediated dilatation
Activation of M3 receptors causes increased secretions:
Increased secretion of:
- Saliva - increase in phospholipase c causes increase in saliva causing increase in
saliva production
- m1 receptors on parotid cells also coupled to phospholipase c so it is the same
mechanism
- Tears - same process for increase in tear production
- Gut acid - M3 receptors on the actual cells that make the gout acid known as parietal
cells
- There are also m3 receptors along with m1 receptors on the cells that store
histamine called entromachromine cells. Histamine is stimulate of gut acid
- Sweat - M3 receptors on sweat glands. - this is sympathetic but it weird because it
uses Ach
Erection of male genitalia
Mediated by filling of the organ with blood as penile arteries and corpus cavernosum relax and fill up with blood
- Spongy tissue fills with blood as well as outflow veins become compressed by hydrostatic pressure
Penile erection - the parasympathetic nerves that innervate the male productive organ Some = non adrenergic non cholinergic ( NANC ) - this neurons release nitric oxide
Some mixed nerves have Ach and NO synthesis
Nitric oxide mediated dilatation that produces the physiological effect - this can be NO working directly on the penile muscle or ach binding to m3 receptors on the endothelium of the penile artery leading to no production smooth relaxation
-
Intro The Cell Regulation14
-
Drug Receptor Interaction11
-
Receptor Mechanism I10
-
Receptor Mechanism II11
-
Receptor Mechanism III15
-
Muscle Contraction16
-
Drugs And Synaptic Transmission10
-
Intro To The ANS15
-
Membrane Potentials14
-
Sympathetic Nervous System21
-
Parasympathetic Nervous System15
-
Drug Absorption7
-
Drug Distribution6
-
Drug Metabolism And Elimination5
-
Pharmacological Modulation Of ANS1
-
Overview Of The Nervous system7
-
Exam Questions10
