GIT HORMONES

DR.NILESH KATE. M.D.

ASSOCIATE PROFESSOR,DEPARTMENT OF

PHYSIOLOGY,

OBJECTIVES INTRODUCTION. HISTORY. CLASSIFICATION. COMMON DESCRIPTION.

CELLS PRODUCING – SOURCE. CLASSIFICATION. LOCATION. STIMULUS. MECHANISM OF ACTION. ACTIONS. APPLIED.

INTRODUCTION Earlier ---Believed Regulatory mechanisms were

controlled by the nervous system

Later numerous chemicals in the name of hormones were found

Hormones -- Play an integral role in most of the regulatory mechanisms in our body

Main objective of learning this topic in detail

INTRODUCTION. (Cont….)

Largest endocrine organ Enteric endocrine system. Total about 30 GIT hormones. These are biologically active

polypeptide & act in a paracrine fashion.

Main function is: 1. To regulate the git secretion 2. To regulate the movement of GI

tract.

PARACRINE HORMONES.

SITE OF ACTION.Endocrine Autocrine Paracrine

HISTORY. BAYLISS & STARLING (1902) discovered the first

GIT hormone secretin. GREGORY AND TRACY (1964) --chemical

definition of Gastrin. YALOW AND BENSON (1966) invented RIA to

estimate quantity . JORPES AND MUTT (1996) chemical nature of

secretin and cholecystokinin and a group of other hormones.

Endocrinal cells.Endocrinal cells. Origin - Neuroectodermal Act - On surfaces Mechanism - 1. Neurocrine 2. Paracrine 3. Classic endocrine

Endocrine cells - GIT“Enteroendocrine cells” More than 15 types present Spread all over --stomach, small

intestine, colon

Many cells secrete only one hormone

eg. G cells, S cells, K cells, M cells

Cells that manufacture Serotonin in addition to polypeptides – Entero- chromaffin cells.

APUD cells or Neuroendocrine cells(Amine Precursor Uptake and

Decarboxylase).

Cells that manufacture amines in addition to polypeptides

Found in lungs and other organs in addition to GIT

Can form carcinoid tumors

GI HORMONES

GASTRIN FAMILY SECRETIN FAMILY OTHERS

1. Secretin2. Glucagon3. Glicentin4. VIP5. GIP

1. Gastrin2. Cholecystokinin (CCK)

1. Peptide YY2. Ghrelin3. Motilin4. Somatostatin5. Neurotensin6. Substance P7. GRP8. Bombesin9. Glucagon10.Guanylin

CLASSIFICATION

GASTRIN.Source: G cells (stomach pyloric antral

region)Flask shaped, granules +Also -- hypothalamus,

Pituitary –ant, intermediate

Medulla, Fetal pancreas,

Nerves --Vagus, sciatic nerves

G cells-secrete gastrin

STRUCTURE:

APUD CELLS polypeptide3 types

G14 G17 G34

G17– Principal formHalf life 2-3 minMetabolised – kidney, SI.

G.I. HORMONES

Structure of Structure of SecretinSecretin (27 AA) (27 AA) (comparison with other GI hormones)(comparison with other GI hormones)

Gastrin (17 AA)Gastrin (17 AA)Cholecystokinin (CCK (33 AA))Cholecystokinin (CCK (33 AA))

LOCATION.

STIMULATION FOR RELEASE

STIMULATION HORMONES RELEASED

VAGAL STIMULATION, HCL & PRODUCT OF DIGESTION

GASTRIN

DIETARY PROTEIN GASTRIN & CCK

DIETARY CARBOHYDRATE GIP & GLUCAGON LIKE SUBSTANCES

DIETARY FAT CCK & GIP

HYDROGEN IONS SECRETIN

• “TASTE” – the luminal environment & Respond

STIMULATION OF GASTRIN Stimulation increases

Luminal * peptides & amino acids- phenylalanine & tryptophan* Distention of pyloric antrum.Heidenhain pouch – denervated antral pouchPavlov pouch – small pouch with intact nerve & blood supply.

Neural * vagal through GRP

Blood borne* Calcium * Epinephrine

DECREASESDECREASES

Luminal

* Acid – by negative

feedback effect

* Somatostatin

Blood borne

Secretin

VIP, GIP

Glucagon

Calcitonin

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Mode of actionGastrin Receptor (parietal cells)

Intracellular calcium(IP3) H+-K+ ATPase Ca++ activates

protein kinase

Acid secretion

Function of gastrin. Stimulate Gastric Acid and pepsin

secretion Trophic action – growth of gastric

mucosa and intestinal mucosa Stimulate Gastric Motility Contraction of muscle at gastro

esophageal junction cardiac sphincter prevents reflux oesophagitis Peristaltic

contraction

Functions of Gastrin. Stimulate Exocrine pancreas secretion Stimulate Insulin secretion Stimulate mass movement of large intestine Colonic contraction that initiates Gastro-colic

reflex – defecation after meal Stimulate Histamine secretion from ECL cells

Food in the stomach (gastric distension)

Products of protein digestion (peptides and amino acids)

Vagal stimulation(Non – cholinergic)

G cells of stomach

Secretion of gastrin

Parietal cells of stomach

HCI secretion

High acidic gastric content(auto regulation of gastrin secretion

Acidic duodenal chyme(secrete hormones)

Intestinal hormones(GIP, VIP, somatostatin, secretin

& glucagon)

REGULATION

CHOLECYSTOKININ-pz.

GREEK –

chole, "BILE"; cysto, "SAC"; kinin, "MOVE"; so MOVE THE BILE-SAC

Source: I cells – Granular mucosal cells of duodenum & jejunum.

Also – cerebral cortex, somatic nerves, distal ileum, colon.

STRUCTURE:

CCK 58 39 33 12 8 4

Stimuli: Acid, protein, fat Digested products in duodenum

Initially considered 2 hormones later found to be one

Functions of CCK-pz Contraction of gall bladder –

increased bile release Stimulate pancreatic secretion

rich in enzyme Augments the action of secretin Inhibit gastric acid secretion Inhibit gastric motility Delay gastric emptying

Regulation of secretions.

•CCK-PZ –• Increased by

Acid in duodenumProducts of carbohydrates, fats, & proteins digestion. Mainly peptides & amino acidsPositive feedback–

SECRETIN.Bayliss & Starling (1902)

discovered the first gastro intestinal hormone SECRETIN

SOURCE : S cells – upper SI (Argentaffin cells)

Structure : 27 AA

Stimuli : Acid in duodenum

Function of secretin.

Stimulate secretion of pancreatic juice rich in HCO3

-

Stimulate bile secretion. Augment action of CCK to produce pancreatic

secretion rich in enzymes Reduces the gastric acid secretion and

motility Contraction of pyloric sphincter

HCL & MOTILITY

NaHCO3

HCL +NaHCO3Nacl , CO

2 , H2 O

REGULATION OF SECRETION

GASTRIC INHIBITORY PEPTIDE( GIP)

Source: K cells – jejunum & duodenum

Initially called Enterogastrone. Discovered as a factor in extracts of

intestine that inhibited gastric motility and secretion of acid.

GASTRIC INHIBITORY PEPTIDE( GIP)

Another activity of GIP is its ability to Enhance the release of insulin in response to infusions of glucose. -- Glucose-dependent insulinotropic peptide.

Regulation – Increases by fat in duodenum

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Source – Mucosal cells in jejunum

Stimuli – fatty meal

Structure -- polypeptide 28 amino acids

Other sites— Nerves in GIT, Blood, Brain ( cerebral cortex) Autonomic nerves.

VASOACTIVE INTESTINAL POLYPEPTIDE (VIP)

Stimulate Intestinal secretion of electrolytes & water.

Vasodilatation – decreases BP Induce smooth muscle relaxation (lower

esophageal sphincter, stomach, gallbladder) Stimulate secretion of water into pancreatic

juice and bile. Inhibition of gastric acid secretion and

absorption from the intestinal lumen. Decreases the GI motility.

ACTIONS.

ENTEROGLUCAGON AND ENTEROGLUCAGON AND GLUCAGON-LIKE PEPTIDES. GLUCAGON-LIKE PEPTIDES.

Source : Terminal SI and LI - L cells.

Given the name "Enteroglucagon", "Proglucagon-

derived Peptides". In both pancreas and gut, 3 types of products are

generated: • Glucagon-like Peptide-1 (GLP-1)• Glucagon-like Peptide-2 (GLP-2)• Glucagon-like Peptide-3 (GLP-3)

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GLP-1GLP-1 Inhibit gastric

emptying, Inhibit gastric

secretion and Inhibit pancreatic

secretion, Decreases food

intake.

Glucagon-like peptide-2

It stimulates proliferation of intestinal epithelial cells.

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SOMATOSTATIN (GHIH). Source -- S Cells or δ cells

GIT MUCOSA.

Structure– SS14, SS28 (more active)

Somatostatin is also secreted by the Hypothalamus & pancreas.

Stimuli – Acid in stomach stimuli which increases insulin secretion

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ACTIONS Secretions of Gastrin, secretin, Motilin,

Pancreatic – Exocrine & Endocrine secretions

Gastric acid secretions & motility ( Dyspepsia & slow gastric emptying)

Gall bladder contractions ( Precipitate gall stone)

Absorption of glucose amino acid, & triglyceride.

MOTILIN

• Source -- Endocrinocytes (Mo Cells) in the mucosa of the proximal Small Intestine.

• Based on 22 AA sequence,

MOTILIN participates in controlling the pattern of smooth muscle contractions in the upper GI tract that increases the MIGRATING MYOELECTRIC COMPLEX ("Housekeeping contractions“).

It sweep the stomach and SI clear of undigested material and stimulates the production of PEPSIN.

GHRELIN-28 AA ’Ghre’’ – Growth ---- Europian name. Source -- Endocrine cells in the stomach,

especially when one is hungry; Action-- acts on the hypothalamus to stimulate

feeding;

This action counteracts the inhibition of feeding by leptin and Pyy 3-36.

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GHRELIN-28 AA

GUANYLIN 15 amino acid residues Source: Cells of the intestinal mucosa Stimulant: Stimulation of Guanylin Function: It increase Cl- movement to intestine

Other hormonesHormonesHormones sourcesource EffectsEffects

Neurotensin Neurotensin Neurons & ileal Neurons & ileal epitheliumepithelium

Inhibit GI motility - ileal Inhibit GI motility - ileal blood flowblood flow

GRPGRP Vagal nerveVagal nerve Gastrin releaseGastrin release

GuanylinGuanylin Paneth cellsPaneth cells Secretion of chloride ionsSecretion of chloride ions

ChymodeninChymodenin Duodenal mucosaDuodenal mucosa Selective secretion of Selective secretion of chymotrypsinogen from chymotrypsinogen from pancreatic acinar cellspancreatic acinar cells

Substance PSubstance P Entire GIT Entire GIT Increases the motility of SIIncreases the motility of SIIncreases local vasodilationIncreases local vasodilationPerception of pain sensationPerception of pain sensation

BombesinBombesin Entire GITEntire GIT Increases gastric secretionIncreases gastric secretionIncreases motility of gall Increases motility of gall bladderbladderIncreases motility of SIIncreases motility of SI

SUMMARY OF ACTIONS

SUMMARY

APPLIED PHYSIOLOGY.

ZOLLINGER-ELLISON SYNDROME (GASTRINOMA)

ULCER

Zollinger-Ellison Syndrome (Gastrinoma)

Caused by a tumor (or tumors) called

Gastrinoma gastrin stomach acid.

SIGNS & SYMPTOMS:Pain in the stomach and esophagus,NauseaVomiting of blood, Difficulty in swallowing Sore throat, coughing, and wheezing Sour or bitter taste in the mouth Blood in the stool

VERNER MORRISON SYNDROME ( VIPOMAS)

VIP Cause profound and chronic WDHA-syndrome (or) pancreatic cholera syndrome Watery Diarrhoea and resultant

Dehydration, Hypokalemia, Achlorhydria, Acidosis,

vasodilation (flushing and hypotension),

Hypercalcemia Hyperglycemia.

VERNER MORRISON SYNDROME

TREATMENTSymptomatic

control Somatostatin

analogues Resection

CARCINOID TUMORS( APUDOMAS) Carcinoid tumors originate from the diffuse

neuroendocrine system, specifically the enterochromaffin (EC) cells (submucosa of the intestine)

Gastrointestinal Peptides and Amines Secreted by Carcinoid Tumors

ACTH Gastrin Pancreatic polypeptide Insulin Vasoactive intestinal polypeptide (VIP) Serotonin 5-hydroxyindoleacetic acid

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SUMMARY INTRODUCTION HISTORY COMMON DESCRIPTION

CELLS PRODUCING CLASSIFICATION LOCATION STIMULUS MODE OF ACTION

DETAIL ABOUT EACH HORMONES GASTIN CHOLECYSTOKININ SECRETIN MOTILIN VASOACTIVE INTESTINAL

POLYPEPTIDE GASTIC INHIBITORY

POLYPEPTIDE GLUCOGAN LIKE PEPTIDE OTHER HORMONES

Thank You

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