Hormones of GIT

Humoral agents (biological active polypeptides)secreted by cells in mucosa and transported in the circulation to influence functions of stomach, intestines, the pancreas & gall bladder.

Act in a paracrine fashion.

Regulation of GIT

Gastrointestinal Hormones• Biologically active polypeptides• Secreted by;

i. nerve cells &ii. gland cells in the mucosa of G.I.T

Enteroendocrine cells: (G cells or S cells)> 15 types of cells identified in mucosa of stomach,

small intestine & colonAPUD cells (Amine Precursor Uptake & Decarboxylase cells) or neuroendocrine cells found in lungs & GIT; form carcinoid tumors.

• Regulate;* Secretions &* Motility of GIT

Gastrointestinal Hormones• Classification:

1. On the basis of structural & functional similaritya. Gastrin Family: Gastrin, CCKb. Secretin Family:Secretin, Glucagon

Glycentin (GLI)VIP & GIP

2. Other GI HormonesNeurotensin GlucagonSubs P GhrelinGRP GuanylinBombesin UrogastroneSomatostatin

GastrinProduced by: G-cells (flask shaped) of antral mucosa of

stomach.Respond to changes in gastric contents Receptors of gastrin are present on microvilli

During fetal life Gastrin is found in pancreatic islets.Also found in Ant & Int lobes of Pituitary, Hypothalamus,

Medulla, Vagus & Sciatic nerves.

Types: i. ‘Little’ Gastrin; Principal form, G17 i.e.17 A.AcidsSecreted by G-Cells of gastric antrum

in response to meal.ii. ‘Big’ Gastrin; G34 i.e. 34 A. Acids

Secreted between meals

FunctionNot known

Secretion of GastrinStimuli that increase Gastrin secretioni. Luminal: Protein meal (Peptides & A. Acids)

Distentionii. Neural: Increased vagal discharge via GRP

iii. Blood borne: ↑ Calcium↑ Epinephrine

Stimuli that decrease Gastrin secretioni. Luminal: Acid (low pH) in antrum

Somatostatinii. Blood-borne: Secretin, GIP, VIP, Glucagon, Calcitonin

• Inactivated: In kidneys, S & L. intestines.• Actions:

a. Secretion of Gastric acid, Pepsinb. Stimulation of Gastric Motilityc. Contraction of Gastro-Esophageal sphincterd. Trophic action: Growth of mucosa of

stomach, S & L intestines. e. Insulin secretion

• Gastrin secreting tumor or Gastrinoma(Zollinger - Ellison syndrome)

usually in non-beta-cell pancreasSign & symptoms attributed to gastrin i.e. duodenalulcers, steatorrhea.

GASTRIN

• Now CCK• Secreted by:

I-cells of duodenal & jejunal mucosa in response tobreakdown products of prot, fats in duodenum i.e.a. monoglycerides & fatty acids (not TGs)b. small peptides & a. acids.

• Secreted as: prepro CCK (i.e. CCK58,CCK39, CCK33, CCK12, CCK8)

Also found in nerve cells of distal ileum & colon.

Mostly

Cholecystokinin-Pancreozymin (CCK- Pz)

Functions:• Contraction of gallbladder with relaxation of

sphincter of Oddi• Secretion of pancreatic juice rich in enzymes

e.g. lipase, amylase, proteases • CCK augments the effect of secretin on the secretion of

HCO3- from pancreas ( Alkaline) • Inhibits gastric motility by contraction of pyloric sphincter

( gastric emptying time, ensuring adequate time for digestion & absorption of fats)

• Motility of s.intestine & colon• Secretion of enterokinase.

Cholecystokinin

SecretinSecreted by:

S-cells of mucosa of s.intestine only one form exists.

Actions: Secretion of HCO3

- by ducts of pancreas & biliary tract to neutralize H+ in small intestine(essential for fat digestion; as the optimum activity of pancreatic lipase is between pH 6-8, denatured at pH < 3)

Gastric secretion Contraction of pyloric sphincterStimulated by:Products of prot. digestion & acid (when pH < 4.5)

• GIP (Gastric Inhibitory Peptide):

• VIP (Vasoactive Intestinal Peptide):Source: Neurons of mucosa & smooth muscle

Secreted by: K-cells in mucosa of duodenum/Jejunum

Stimulated by: Oral glucose ,Fatty acids,A. Acids in duodenum.

Actions: ↑ insulin secretion from pancreatic β-cells

Actions:Stimulates intestinal secretion of electrolytes & H2O↑ Pancreatic secretion Inhibits Gastric secretionsRelaxation of Int. Smooth muscles& Bl.vessels.

• GRP (Gastrin Releasing Peptide) or Bombesin:

Secreted by: Neurons of Gastric mucosa

Action: ↑Gastric secretion

• Substance P:Cosecreted with Ach

Actions:Contraction of smooth muscle↑ Salivary secretion

K-cellsNeurons

G-cells

S-cellsI-cells

GRPNeurons