Neural Control of Motility and Gastric Secretion

A lot of this lecture was a recap of PHYL2001, but let's face it, we probably need the refresher.

Neural Control of the Gut

I've already written a fair bit about neural control of the gut in my previous post, but now it's time to get into some more detail!

Firstly, neural control of the gut isn't just limited to reflexes from our autonomic nervous system. Higher brain centres might also be involved, as studies have found that more acid is generated when we eat tasty food compared to eating simple gruel. These higher brain centres, however, often work via sympathetic and parasympathetic centres. Fun fact: the parasympathetic motor control centre is located close to the respiratory motor centre. Is this significant? No idea. Moving on...

A special property of enteric neurons is that they have prolonged excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs). If I remember correctly, our lecturer said that the record is something like 10 minutes of activation following stimulation. The long duration is due to GPCRs, not ion channels, being the main post-synaptic receptors (as we shall see later). The main receptors include muscarinic cholinergic receptors for ACh, NK receptors for substance P, and μ and δ opiate receptors for enkephalins, but there are many others. ACh and substance P stimulate contraction, while enkephalins, VIP (vasoactive intestinal peptide), and NO inhibit contraction. Interestingly enough, while VIP inhibits contractions, it also stimulates secretions. Sympathetic transmitters can contract sphincters via α-receptors, and relax other tissues via β-receptors.

Control of peristalsis is a little bit complicated. Stretch receptors can synapse to two different kinds of interneurons. One type of interneuron signals via ACh to an inhibitory neuron, relaxing distal circular muscle. Relaxing this muscle opens up some room for the food to move through. Another interneuron signals via 5HT (serotonin) to some excitatory neurons. One neuron contracts proximal circulatory muscle, pushing the food along, and another neuron contracts distal longitudinal muscle, pulling the gut along. Peristalsis only occurs over a small area, as tonic inhibition via inhibitory nerves prevents spread of peristalsis to other areas. Therefore, while slow waves spread throughout the gut, action potentials do not.

Motility of the intestine

Between meals, the intestines display a Migrating Motor Complex (MMC) pattern. This consists of peristaltic aboral movement over short sections of the gut. (Aboral basically means "away from the mouth.") MMC helps to prevent the accumulation of bacteria and get rid of any undigested stuff remaining in the intestines. During a meal, vagal reflexes (possibly triggered by receptors in the gut) start the mixing phase which, as its name suggests, mixes things. Neural reflexes, hormonal and paracrine transmitters may all play roles in this phase.

Control of acid secretion

See previous post: Gastrointestinal Function part 1

This is going to be a bit messy, but I'm just going to try and fill you in on some details that I didn't mention in the above post. Let's start with a few dot point fun facts:

• Most of the cells involved in acid secretion are found in crypts in the stomach. These crypts are also called the Crypts of Lieberkühn gastric pits (I've since learned that the Crypts of Lieberkühn are a feature of the intestines, not the stomach- whoops!). D cells, or antral somatostatin cells, which inhibit acid secretion, are also found here.
• Gastrin stimulation is enhanced not only by amino acids, but also by vagal stimulation (via gastrin-releasing peptide, not just ACh) and antral distension (via the vago-vagal reflex).
• Gastrin not only stimulates acid secretion, but also stimulates histamine release from ECL cells.
• Antral somatostatin cells (a.k.a. D cells) have long projections (kind of like nerves but not) and microvilli on their cell bodies.
• There are two types of D cells: antrum and corpus. Antrum D cells face the lumen, whereas corpus D cells are kind of buried. Antrum D cells can directly detect the lumen pH. Corpus cells can't, but they might be activated through paracrine action or some other mechanism.
• Gastrin stimulates somatostatin release, and somatostatin inhibits gastrin release. Kind of like a negative feedback system.
• Somatostatin not only inhibits G-cells, but also inhibits acid secretion from parietal cells and histamine release from ECL cells.

Now let's get into some more detail about acid secretion! As mentioned in that post linked to above, parietal cells have intracellular canaliculi with H⁺/K⁺ pumps. The canaliculi expand when the cell is stimulated. Where does the H⁺ come from? It comes from the breakdown of CO₂ into H⁺ and HCO₃^- by our good friend carbonic anhydrase. HCO₃^- then exits the cell via a HCO₃^-/Cl^- antiport in the basolateral membrane. Cl^- exits the cell through uniporters on the apical side of the membrane, so essentially these cells are secreting HCl (H⁺ through the pumps, Cl^- through the channels).

Ready for even more detail? I hope you remember the smooth muscle contraction pathways, because believe it or not, they're somewhat relevant again! M₃ receptors, which respond to ACh, and CCK_B receptors, which respond to gastrin, are both G-protein coupled receptors that work via Gq and phospholipase C. As you should hopefully recall, this leads to activation of phospholipase C and the production of IP₃. IP₃ induces Ca²⁺ release from the endoplasmic reticulum, and this calcium goes on to interact with calmodulin. So far, everything has been the same as in smooth muscle, but now we're going to get really radical and diverge a bit. In parietal cells, Ca-Calmodulin activates calmodulin kinase (CalM Kinase). CalM Kinase phosphorylates and activates the H⁺/K⁺ pump.

Histamine is a little bit different. Histamine acts on the H₂ receptor, which works via G_s. G_s activates adenylate cyclase, which catalyses the production of cAMP. cAMP activates protein kinase A (PKA), which phosphorylates and activates the H⁺/K⁺ pump (at a different site to CalM Kinase).

The last point that I want to touch on is the protective barrier. Mucous cells have a Na⁺/HCO₃^- pump on their basolateral membrane. The HCO₃^- pumped in comes from parietal cells (remember that HCO₃^-/Cl^- antiport that I mentioned earlier?). HCO₃^- then enters the lumen via channels in the apical membrane. The main function of HCO₃^- is to neutralise the stomach acid, preventing the stomach from eating itself.