Regulation of gastric secretion and the role of pharmacological modification
1. Understand the structural and functional features of cells and cell
membranes which allow movement of ions and molecules into and across
cells
The cell membrane is the principal structure which regulates movement of
ions/molecules into the cells cytoplasm and across cells into the ECF. The structure
of the cell membrane is referred to as a ‘fluid mosaic model’ as it is compromised of
a lipid bilayer. The lipid molecules (mostly phospholipids) that make up the
membrane have a polar, hydrophilic head and two hydrophobic hydrocarbon tails.
When the lipids are immersed in an aqueous solution, the lipids spontaneously align
the tails together and leave the hydrophilic heads exposed. This arrangement
creates a very flexible and fluid- like character. The mosaic refers to the membrane
proteins that serve various functions such as transport channels, enzymes, antigens
and receptors.
Ability of the ions/molecules to move across membrane depends on their size,
hydrophilic/hydrophobic properties and the electro-chemical gradient of across the
membrane.
3 major transport mechanisms:
DIFFUSION
-Movement of
molecules from
highlow conc.
over a conc.
gradient.
-Does not require
membrane proteins
-E.g. Water, and
small non-charged,
non-polar molecules
CARRIERMEDIATED
TRANSPORT
Two ways:
VESICULAR
TRANSPORT
-Facilitated
diffusion with help
of membrane protein
to assist polar
molecules. No
energy required.
Helps transport a
solute down
concentration
gradient that can’t
normally pass, such
as a glucose
-Endocytosis (bring
matter into the cell)
Two ways:
-Excoytosis
(release matter from
a cell)
molecule.
-Active transport.
ATP energy
dependent as
moving molecule up
its concentration
gradient. For eg the
sodium-potassium
pump.
2. Describe in outline the hormonal and nervous control of the stomach

Good animation: http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter24/animation__three_phases_of_gastr
ic_secretion.html
Stimuli acting at 2 distinct sites (head, stomach and small intestine) provoke or inhibit
gastric secretory activity in the three phases of gastric secretion. The effector site is
the stomach in all cases and the three stages once initiated can work concurrently:
Phase 1: Cephalic
-occurs before food enters stomach preparing it for food
-few minutes long
-triggered by aroma/taste/site of food
-Input to olfactory receptorspreganglionic fibres in vagus nerve stomach glands
-stimulates mucous for pepsinogen and gastric acid production
Phase 2: Gastric
-initiated when food enters the stomach in 2 ways:
1. Stretching the stomach
2. Raising pH of contents
-stretching activates myenteric and vagovagal reflexes stimulating gastric secretion
-also stimulated by Ach, histamine and gastrin
-3-4 hours long
Phase 3: Intestinal
-duodenal response to chyme by moderating gastric activity by hormones and
nervous reflexes
-duodenum initially enhances gastric secretion but then inhibits it in two ways:
1. acid and semidigested fats in the duodenum trigger an enterogastric reflex
which sends inhibitory signals to stomach.
2. secretin, GIP and CCK hormones also inhibit gastric secretion and motility
allowing duodenum to process chyme already in it
3. Identify the roles of gastrin, histamine, secretin, gastric inhibitory
peptide, and acetylcholine in control of gastric acid secretion and motility
Hormone/neurotransmitter Target organ
Gastrin
Mainly stomach
but some effect
on small intestine,
ileocecal valve
and large intestine
Activity
Stomach: ↑ acid
secretion, ↑
gastric motility
(stomach
emptying). ↑
enzyme secretion
Small Intestine: ↑
gastric motility
ileocecal valve:
relaxes valve
Large intestine: ↑
gastric motility
Histamine
stomach
Secretin
Stomach,
pancreas and
liver
↑ acid secretion
and ↑ blood flow
Stomach: ↓ acid
secretion and ↓
gastric emptying
Pancreas:: ↑
pancreatic fluid &
bicarbonate
secretion
Gastric inhibitory peptide
Stomach
Acetylcholine
Stomach
liver: ↑ bile output
↑ insulin release
↓ acid secretion
↓ gastric motility
↑ acid secretion ↑
blood flow ↑
mucus secretion ↑
bicarbonate
secretion
3. Outline the site and mechanism of action of the H2 receptor antagonists
-H2 receptor antagonists work on the histamine receptors in the stomach mucosa to
effectively reduce HCL acid secretion by parietal cells by up to 90%. These drugs
compete with histamine for H2 receptors in a reversible reaction, so when their use
is withdrawn acid secretion will reoccur and affect patients with history of duodenal
ulcers.
-Effective to alter basal acid secretion and secretion induced by food either
anticipation (vagal) and food consumption.
-Most prominent effect however on basal acid secretion.
5. Indicate other sites for pharmacological intervention in peptic ulcer disease
(proton pump inhibitors, antacids)

Proton pump inhibitors
-Blocks H+/K+ ATPase on parietal cells inhibiting gastric acid secretion at the terminal
stage.
-Inhibits both basal and stimulated acid secretion.
-Faster acting and more effective than H2 antagonists.

Antacids
-These are weak bases that act by neutralising gastric acid in the lumen of the
esophagus, stomach and duodenum. They are used to relieve gastric pain and cell
erosion caused by excessive acid secretion.
-Most commonly used and effective is magnesium hydroxide

Prostaglandins
-Prostaglandins produced in the gastric and intestinal mucosa are effective in
reducing acid secretion. Prostaglandins also protect deeper mucosal cells from
damage.
-Prostaglandin analogues (misoprostol) inhibit histamine-mediated stimulation of acid
secretion. However, they are clinically mainly used to prevent gastric damage from
chronic use of NSAIDS.

Muscarinic receptor antagonists
-Muscarinic receptor antagonists reduces the activity of the muscarinic acetylcholine
receptor (namely M2) by competitively blocking the receptor site from Ach.
-M2 receptors found on many locations within the gastrointestinal tract).