hormones of the GI system Flashcards

1
Q

clear cells

A

produce amines and peptides

endocrine cells in this category

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2
Q

open configuration

A

most endocrine cells of gastroentero-pancreatic system, except for those in the pancreas and oxyntic region of the stomach
have both a luminal and serosal face
enables cells to be more easily affected by luminal factors
gives the cells the potential for exocrine as well as paracrine and endocrine functions

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3
Q

families of GEP hormones

A

secretin and gastrin

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4
Q

peptides in secretin family

A

vasoactive intestinal polypeptide (VIP)
gastric inhibitory polypeptide (GIP)
pancreatic glucagon
gut glucagon-like immunoreactivity (GLP-1)
bombesin (aka gastrin releasing peptide (GRP)

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5
Q

bombesin (gastrin releasing peptide, GRP)

A

originally isolated in skin of amphibians

vagal transmitter that accounts for release of gastrin seen following vagal stimulation

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6
Q

peptides in gastrin family

A
gastrin
cholecytokinin (CCK)
motilin
enkephalin
cerulein (in amphibians)
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7
Q

GEP hormones that don’t fall into gastrin or secretin families

A
pancreatic polypeptide (PP)
somatostatin (SRIH)
uragastrone
chymodenin (also secretin)
tachydinins
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8
Q

gastin family characteristics

A

size homology

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9
Q

gastrin

A

in gastrin family
has 4 major forms in the circulation
largest form = component I = likely preprogastrin or part of gastrin precursor
big gastrin = 34 AA
this followed by 17 AA form and 14 AA form
each exists in sulfated and nonsulfated forms - doubles number of variants
total of 20 or more variants

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10
Q

scheme proposed for purpose of multiple strains of gastrin

A

component 1 = preprogastrin
cleaved enzymatically in cells to 34 AA form = progastrin
cleavage of this gives 17 AA form - most active on molar basis
further cleavage => 14 aa form

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11
Q

pentagastrin

A

form of gastrin most often clinically known
synthetic pentapeptide containing C-terminal of gastrin, beta-alanine, and tertiary butyloxycarbonyl (tBOC = N-terminal blocking agent)

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12
Q

cholecytokinin

A

has some size heterogenity
primary circulating form has 33 AA residues
39 AA molecule also exists
small fragment - c-terminal octadecapeptide - has most of its biological activity
may be neuronal and act as NT

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13
Q

what will diminish the activity of gastrin and CCK

A

deamidation of C-terminal residue

removal of sulfate groups

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14
Q

secretin

A

requires all of its 27 AA residues to maintain biological activity

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15
Q

major physiological roles of gastrin

A

1: stimulation of gastric acid from oxyntic cells - can lead to increased release of pepsinogen from chief cells
2: a trophic action on the mucosa of the stomach
3: stimulation of gastric motility

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16
Q

gastrin and gastric acid secretion (synergism)

A

works synergistically with AcH and histamine

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17
Q

ACH on gastric acid secretion

A

works synergistically with Ach

generated from vagal impulses

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18
Q

histamine on gastric acid secretion

A

acts through type 2 histamine receptors
works synergistically with gastrin
can be blocked by cymetidine

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19
Q

cymetidine

A

blocks effects of histamine and acetylcholamine on oxyntic cells and so blocks gastric acid secretion
used to treat ulsers
but also blocks histamine type 2 receptors in brain

20
Q

control of release of gastrin

A

stimulated by peptide digestion products of food and by vagal activity
AA in chyme, especially Tryp, Phe, and Arg can also stimulate release
release inhibited by acid, secretin
gastrin action inhibited by cholecystokinin (CCK)

21
Q

vagal activity in gastrin release

A

produces transmitter GRP (gastrin releasing peptide/bombesin)
accounts for all vagus-stimulated gastrin release

22
Q

negative feedback for gastrin release

A

inhibited by acid
when pH outside antral mucosa falls below pH 3.5, gastrin release turned off
indirect mechanism through acid stimulated release of somatostatin

23
Q

atrophic gastritis

A

chronic decrease in the output or function of oxyntic cells

often have extremely high circulating levels of gastrin because negative feedback mechanism is missing

24
Q

zollinger-ellison syndrome (ZE)

A

gastrin hypersecretion from pancreatic islet tumors (gastrinomas) or from hyperplastic mucosal G cells
results in gastric acid hypersecretion and ulcerative disease
also excessive overgrowth of gastric mucosa => additional acid production
diagnostic test: when secretin administered to patient with Z-E syndrome, causes increase in circulating gastrin levels - should inhibit

25
Q

physiological effects of cholecystokinin (CCK)

A

1: stimulation of pancreatic proenzyme release
2: contraction of the gall bladder
3: relaxation of the sphincter of oddi
4: reduction of gastrin-induced acid secretion by competitive inhibition
5: important synergistic action with secretin on release of pancreatic HCO3-/H2O release

26
Q

release of cholecystokinin (CCK)

A

major factors: peptides and certain AA from digestion of foods
most potent stimulators = tryptophan and phenylalanine
others = maline, leucine, and methionine
fats and acidity weak stimulators

27
Q

targets of cholesystokinin (CCK)

A

acts directly on acinar cells of the pancreas and on the muscle of the gall bladder
effects on intestinal muscle mediated through release of AcH

28
Q

what can CCK be used to diagnose?

A

pancreatic and gall bladder disease
stimulatory effects on intestinal muscle used in roentgenological investigations of the intestine
has limited applicability theraputically but can be used to eliminate obstructions from the bile duct without surgery

29
Q

physiological roles of secretin

A

1: stimulation of pancreatic water and bicarbonate secretion into the duodenum - synergizes with CCK
2: inhibits acid secretion by gastrin by inhibiting the release of this peptide
3: acts synergistically with CCK in promoting release of pancreatic enzymes, flow of bile, and the composition of bile (increases H2O/HCO3- content)

30
Q

release of secretin

A

stimulated by the introduction of acid into the upper small intestine
not dependent on neuronal innervation but its action on the pancres are reduced by vagotomy

31
Q

use of secretin in diagnosis

A

in examination of pancreatic function

for zollinger-ellison syndrome

32
Q

glucagon-like peptide I (GLP-1)

A

most potent stimulator of insulin release from the pancreas, esp. in response to orally ingested glucose
intake of glucose increases release of GLP-1 => increased insulin levels in the protal blood system before glucose blood levels rise appreciably
inhibits gastric secretion and emptying

33
Q

glucagon-like peptide 1 structure and synthesis

A

30 AA peptide

produced by intestinal L cells

34
Q

use of GLP1 clinically

A

anorexogenic

used to treat patients with T2DM

35
Q

ghrelin

A

28 AA
elevated in blood during fasting and insulin-induced hypoglycemia
same as brain/gut peptide growth hormone releasing peptide (GHRP) = stimulates GH release by increasing GHRH release, inhibiting somatostatin release, and having a direct positive effect on somatotrophs in the pituitary

36
Q

leptin

A

protein hormone of adipose tissue - involved in energy balance
activates cell-surface receptors to inhibit the desire to eat = anorexogenic

37
Q

adiponectin

A

protein hormone of adipose tissue - involved in energy balance
activates cell-surface receptors to inhibit the desire to eat = anorexogenic
increases insulin responsiveness in T2DM

38
Q

vasoactive intestinal peptide (VIP)

A

major mode of action may be as a NT
as GI hormone: released by dilute HCl or fat introduced into duodenum
acts with NO in producing sphincter relaxation
can also inhibit gastric acid secretion and motility, inhibit gall bladder contraction, and stimulate water and electrolyte secretion from mucosal surfaces of the intestine and pancreas
tumors that secrete VIP in large amounts (VIPomas) associated with watery-diarrhea syndrome - indirectly supports an effect on mucosal secretion of water and electrolytes

39
Q

gastric inhibitory peptide (GIP)

A

inhibitory effect on gastric acid secretion, pepsin secretion, gastric motor activity - but questions about this
has role in control of insulin secretion (though not as potent as GLP-1)
when exogenously administered, causes increase in circulating insulin level
insulinotropic effect seems directly related to level of plasma glucose
not insulinotropic in presence of basal plasma glucose levels, but intravenous infusion or ingestion of gucose increase circulating levels of immunoreactive GIP
release also stimulated by duodenal perfusion of an AA mixture
gastrin and CCK seem to potentiate this

40
Q

somatostatin

A

hypothalamic peptide - NT in peripheral and CNS
GH release inhibiting
product of D-cells of pancreatic islets and gastric mucosa
inhibits insulin and glucagon release and secretion of gastric acid and release of gastrin, secretin, CCK, GIP, VIP and motilin
release in stomach sensitive to acid in chime and plays a pivotal role in neg feedback control of gastrin release

41
Q

urogastrone

A

epidermal growth factor
has been located to submaxillary glands adn brunner’s glands of duodenum
potent inhibitor of acid secretion

42
Q

enkephalin

A

immunoreactive
in antral stomach, duodenum, ileum, colon, gall bladder, and pancreas
opiate
appears to be generally inhibitory

43
Q

peptide YY

A

36 AA, 18 identical to pancreatic polypeptide, tyrosine residues at amino- and carboxyl- terminals
fat stimulates release
inhibits gastric secretion and emptying - vagal effects

44
Q

peptides of amphibian skin

A

includes: bombesin-like peptides, cerulein, tachykinins

45
Q

bonbesin-like peptides

A

in stomach and upper small intestine of mammals
in category of “peptides of amphibian skin”
biological activities identical to bombesin peptides of amphibian skin
include stimulation of gastric acid, pepsin, gastrin, pancreatic enzymes, and pancreatid peptide
inhibition of gastric and duodenal motility
bonbesin is gastrin-releaseing hormone (GRP) and completely accounts for bagally stimulated gastrin release

46
Q

tachykinins

A

in category of peptides of amphibian skin
resemble substance P of mammals both in structure and activity
stimulate GI motility and exocrine secretions of the pancreas

47
Q

cerulein

A

on category of peptides of amphibian skin
close resemblance with regards to chemical structure to gastrin family
stimulates gastric motility, exocrine secretions of stomach and pancreas, and release of insulin, glucagon, calcitonin, and pancreatic polypeptide