Week 1: Integrated Response to a Meal

Question 1

GTPase Cycle

Answer 1

1. Receptor without ligand. GDP bound to Ga and Gby
2. Ligand binds to receptor and activates GTP-GDP exchange
   - GTP binds to Ga and they dissociate from Gby subunit and from the receptor
3. GTP bound Ga associates with next mediator of signaling cascade
4. Hydrolysis of GTP to GDP permits re-association with Gby subunit complex and receptor

Question 2

How do muscarinic Ach receptors elevate cytosolic diacylglycerol and cytosolic Ca2+?`

Answer 2

• GPCR is M3 ACh receptor
• Gaq/Ga11 bind to and activate phospholipase Cb (signaling effector)
• PLCb hydrolyzes PIP2 (phosphatidylinositol bisphosphate), releasing IP3 (inositol trisphosphate) and diacylglycerol (DAG)
• PIP2 receptor on ER is ligand activated Ca channel, opening permits flow of stored Ca to cytosol

Question 3

Hod do a1 adrenergic receptors elevate cytosolic Ca2+?

Answer 3

• via Gai protein subunit, which binds and activates ADP-ribosyl cyclase
• which converts NAD to cADP-R (cyclicADP ribose), which binds ER ryanodine receptor and a ligand activated Ca channel, releasing Ca2+

Question 4

How do b-adrenergic receptors elevate cytosolic cAMP?

Answer 4

• Gas protein subunit, activates adenylyl cyclase, which converts ATP to cAMP
• Gao and Gai bind to and inhibit adenylyl cyclase

Question 5

Cephalic phase: signals and responses

Answer 5

-signals: Thought, smell, taste, distention, chewing, and swallowing activate salivary glands
-stomach: parasympathetic output to stomach for motility, gastrin release, acid secretion
-pancreas: parasymp. output for salt, water, enzyme secretion
SALIVARY gland
-parasympathetic efferents: release NaCl and water, some amylase and mucin
-sympathetic efferents stimulate release of amylase and mucin and some NaCl and water

Question 6

Signals and responses in Gastric phase

Answer 6

-signals: distention-activation of mechanoreceptors, activation of G cell amino acid receptors (amino acids)
-Responses are parasympathetic, even before food reaches the stomach
Stomach
-vagal efferents: peristalsis, acid secretion, pepsinogen secretion, gastrin secretion
-receptive relaxation and peristalsis
Pancreas
-vagal efferents: NaCl secretion and zymogen (proenzyme) secretion

Question 7

Signals and responses in intestinal phase

Answer 7

• signals: distension (mechanoreceptors), osmoreceptors (anisotonicity), activation of enteroendocrine cells, acid, amino acids, fatty acids, monosaccharides,
• parasympathetics increase intestinal motility
• sympathetics decrease intestinal motility
• distension: depends on intensity
• other responses: mixing and propulsion, coordination of gastric emptying with intestinal processing, coordination of gastric acid secretion with need, neutralization of gastric acid, delivery of bile salts, pancreatic hydrolases and zymogens

Question 8

Gastrin: stimuli and target response

Answer 8

1. produced by G cells in stomach
2. Stimuli:
   - neural: gastrin releasing peptide, Ach
   - distension
   - amino acids and peptides detected by local peptide sensor
   - inhibited by low pH
3. Target cells and response
   - gastric parietal cells increase acid secretion
   - gastric smooth muscle increases motility

Question 9

Secretin: stimuli and target response

Answer 9

1. produced in small intestines
2. stimuli: acid
3. target cell and response
   - pancreatic ducts: bicarbonate secretion
   - hepatic ducts: bicarbonate secretion
   - pancreatic acini: potentiates response to CCK, enzyme and NaCl secretory
   - stomach: decreases emptying and decreases acid secretion
   overall: bicarbonate secretion, which is potentiated by CCK

Question 10

Cholescytokinin (CCK)

Answer 10

1. produced in small intestines
2. Stimuli
   - amino acids and fatty acids
3. target and response
   - pancreatic acini: enzyme and NaCl secretion
   - pancreatic ducts: potentiates bicabonate secretory response to secretin
   - hepatic ducts: potentiates bicarbonate secretory response to secretin
   - gallbladder: contraction to secrete bile
   - stomach: decreases gastric emptying
   overall: enzyme and NaCl secretion, potentiated by secretin. Helps secretin stimulate more bicarb secretion

Question 11

Role of enterochromaffin like cells (ECL cells)?

Answer 11

• gastrin release stimulates ECL cells to release histamine

- histamine binds to H2 receptors on oxyntic cells (parietal cells) to stimulate acid secretion

Question 12

Gastric inhibitory peptide (GIP) and glucose dependent insulotropic peptide: stimuli and target response

Answer 12

1. produced in small intestines
2. stimuli:
   - fatty acids and monosaccharides
3. Major target cell and response
   - gastric parietal cells: decreases acid secretion. Don’t need acid to digest carbs/starch.
   - pancreatic islets: potentiates insulin release in response to glucose

Question 13

Local gastric reflexes

Answer 13

1. distension: oxynto-oxyntic, pyloro-pyloric, pyloro-oxyntic, oxynto-pyloric
   - (site of distention-site of response)
   - G cells most abundant in pyloric region
   - oxyntic cells most abundant in corpus?
2. low pH inhibits gastrin release
3. Amino acids: buffer acids, reverse low pH inhibition, activate G cells