Effect

1
Effect Sites of Action of Different Agonist
Drugs on The Isolated Rabbit Intestine

• Lab 2

2
Intestine

• Intestine is composed of duodenum, jejunum
  ileum
• It is a smooth muscle has myogenic contraction
• Spontaneous rhythmic contraction

3
Autonomic nervous system innervations of the
intestine

• Sympathetic

• Parasympathetic

CNS AG e
CNS AG
PGF PostGF
PGF PostGF
Key AG autonomic ganglion E effector
organ PGF preganglionic fiber POSTGF
postganglionic fiber
4
Autonomic nervous system innervations of the
intestine

• Sympathetic
• Transmitter NA, Adrenaline
• Receptors
• (intestine) adrenergic
• a1, b2
• Action
• (intestine) inhibitory (?cont.)

• Parasympathetic
• Ach
• cholinergic
• a-central-Nicotinic (Nn)
• b-periphral-muscarinic(M3)
• excitatory (?cont.)

5
Stimulants

• 1- Autonomic Cholinergic stimulants (Spasmogenic)
• A- Central nicotinic neuronal (Nn) R agonist
  (ganglionic stimulant)
• Dil. Nicotine
• B- Muscarinic receptors agonist M3
  (cholinomimetic)
• Ach its derivatives
• Naturally occurring alkaloids e.g. Pilocarpine
• 2- Direct acting stimulant
• e.g. Bacl2

6
Stimulants

• 1- Autonomic Cholinergic stimulants (Spasmogenic)
• A- Central nicotinic neuronal (Nn) R agonist
  (ganglionic stimulant)
• Act Nn R present in autonomic ganglia
• Ex. Small dose of nicotine ( dil. Nicotine)
• MOA of dil.nicotine
• Dil. Nicotine stimulates Gs protein
  activates Nn R
• ? activates Na-K channels ? rapid ?
  intracellular Na
• ? depolarization ? contraction

7
Stimulants

• B- Muscarinic receptors agonist (cholinomimetic)
• Act on muscarinic M3 receptors
• Ex. 1- Ach its derivatives e.g. methachloine,
  bethanecol, carbacol
• 2- Naturally occurring alkaloids
  e.g. Pilocarpine
• MOA of Ach
• Ach stimulate Gs protein activates M3 R
  ? activation of Phospholipase C enzyme (PLC)
• Splitting of phosphatidylinositol biphosphate
  (PIP2) into
• 1- DAG (diacylglycerol) ? ?opening of
  Calcium channels
• 2- IP3 (inositol triphosphate) ?
  mobilization of Cal. from its stores
• 1, 2 lead to ? intracellular calcium ?
  contraction

8
Stimulants

• 2- Direct acting stimulant
• e.g. Bacl2
• Acts directly on muscle fibers

9
Depressants

• 1- Autonomic adrenergic stimulants (Spasmolytic)
• e.g. adrenaline noradrenaline
• They bind to a1 ß2 receptors causing
  relaxation
• 2- Direct depressants
• e.g. Mgcl2 Papaverine
• Acts directly on muscle fibers