Enteric Nervous System Flashcards
What are enterochromaffin cells?
a subset of enteroendocrine cells that express chromaffin granules and synthesise, store, and release 5-HT
these cells have neuropods which contant terminals of sensory (afferent) neurons and communicate signals with the nervous systems
they have receptors that detect transmitters from the efferent nerve fibers
they have an apical membrane that is in direct contact with the lumen and a basal membrane that is exposed to the lamina propria where neural fibers are located
Neuropods connect with both afferent and efferent fibers
1) Blocking 5-HT uptake back into EC cells with an SSRI –>
2) Blocking 5-HT receptors in the mucosa –>
3) Releasing 5-HT from the mucosa with cholera toxin –>
1) increases segmenting motor activity in the jejunum
2) reduces nutrient-induced segmenting motor activity
3) increases propulsive motor activity
Why is mucosal 5-HT considered a sensory mediator?
It activates local reflexes in addition to having different effects on the motor activity of the system
There is direct evidence that application of amino acids onto the mucosa can trigger activation of local reflexes via the release of 5-HT or ATP as neurotransmitters
Outline how secretion is controlled by secretomotor neurons (the first group, cholinergic neurons) in the submucosal plexus.
1) ACh is released onto muscarinic receptors found in the **basolateral membrane **of the epithelial cells expressing CFTR
2) This increases the Cl- concentration gradient across the **apical membrane **where the CFTR channel is located
3) It also increases the responsiveness of these enterocytes to non-cholinergic sensomotor neurons that release VIP (this is the other group of secretomotor neurons)
Outline how secretion is controlled by secretomotor neurons (the second group, non-cholinergic neurons) in the submucosal plexus.
1) They release VIP
2) This activates **VIP receptors **in the basolateral surface of the enterocytes
3) Activates adenylyl cyclase which increases cAMP
4) Activates CFTR channels
5) Cl- ions are transported into the lumen via CFTR channels
6) Water & Na+ passively follow into lumen, leading to secretion
Both types of secretomotor neurons are regulated by enteric circuits
Non-cholinergic secretomotor neurons are also modulated by sympathetic nerves
What is one thing that may enhance secretion?
It depends on water from the blood stream, so is enhanced by vasodilation of mucosal and submucosal blood vessels
Secretion is electrogenic while absorption is electroneutral
Outline the process of absorption
1) Na+ is transported from the LUMEN into enterocytes at the tips of the villi and the mucosal surface of the colon
2) This transport is via NHE3 (sodium-hydrogen exchanger) in the apical membrane
3) Transports 1 Na+ for 1 H+ (therefore, electroneutral)
4) But, it does drag water and Cl- with it to the CFTR channel
How does the functionality of enterocytes change as they migrate from the base of the crypts to the tips of the villi?
- Newly differentiated enterocytes at the base of the crypts express more CFTR channels
- During the migration process to the tips of the villi, CFTR expression is gradually lost and the NHE3 transporter becomes more expressed
What causes diarrhoea?
Secretion of water into the lumen»_space; absorption of water from lumen
Could be due to increased transit speed (= less absorption)
Could be due to damage to the mucosal epithelium leading to breakdown of mucosal barrier
What is the relationship between CT (cholera toxin) and 5-HT?
- Exotoxin (cholera toxin) activates adenylyl cyclase
- This releases 5-HT from EC cells
- This increases propulsive contractions that reinforces the effects of diarrhoea
- 5-HT3 antagonists may block the effects of CT on ISNs in some cases
CT can’t just activate mucosa directly because of its size – it doen’t reach the base of the crypts where the CFTR epithelial cells are located and can only act on the cells at the tips of the villi and at that region there is no CFTR so you don’t get hypersecretion
What is the relationship between CT & enteric neurons?
- modifies enteric neural activity by increasing the expression / excitability of myenteric ISNs via a neural mechanism
- application of CT onto mucosa for 90 mins **increases action potentials by ISNs **in response to a stimulus
- these ISNs form recurrent networks that produce positive feedback in the circuit
The effect on myenteric plexus is blocked by putting tetrodotoxin in the lumen of intestine where the CT is found
Also blocked by 5-HT receptors
How do chemical composition and volume affect gut function?
- A high nutrient content favours segmentation over propulsion after a meal
- Large volume triggers propulsive contractile patterns and receptive relaxation
What might prevent contractions in the ENS?
- tetrodotoxin = blocks nerve action potentials but not those of smooth muscle
- antagonists of nitocitin or muscarinic ACh receptors
Ascending neurons (circular muscle) & sensory neurons (longitudinal muscle) release which neurotransmitters?
They release the excitatory neurotransmitters ACh and Substance P
The descending neurons (circular muscle) and sensory neurons (longitudinal) release which neurotransmitters?
The inhibitory neurotransmitters NO and VIP
