Effects and Sites of Action of Different Agonists Drugs (Stimulant or Relaxant)on The Isolated Rabbit Intestine

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Effects and Sites of Action of Different Agonists
Drugs (Stimulant or Relaxant)on TheIsolated
Rabbit Intestine

• 313 PHL
• Lab 2

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The nervous control of intestine

• Intestine
• Is composed of(duodenum,jejunum,ileum) .

• It is a Smooth muscle has myogenic contraction
  (i.e. spontaneous rhythmic contraction).
• N.B this rhythmicity due to its pendular movement.

• Is involuntary muscle undergoes the control of
  autonomic nervous system(sympathetic and
  parasympathetic).

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The intestine innervated by ANS

• Parasympathetic
• Acetylcholine (Ach) .
• Cholinergic
• Central Nicotinic (Nn) .
• and peripheral muscarinic (M3)
• excitatory (?contraction)? contraction

• Sympathetic
• Transmitter noradrenalin mainly, Adrenaline .
• Receptors present in
• (intestine) Adrenergic a1,B2
• Action
• inhibitory (?contraction)? relaxation .

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Types of receptors present in the intestine

• Adrenergic.
• Cholinergic.
• Histaminergic.
• Purinergic.
• Serotinergic.

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Drug Acting on Intestine

• STMULANTS
• They are called Spasmogenic
• DEPRESSANTS
• They are called Spasmolytic

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Stimulant Drugs (Spasmogenic)

• A- Autonomic cholinergic stimulants , act on
• 1- Central Nicotinic Neuronal receptor agonist
  (Nn) R (ganglionic stimulant)
• - Act Nn R present in autonomic ganglia
• e.g. Nicotine (small doses) Diluted Nicotine

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Mechanism of Action

• Diluted Nicotine
• Dil.Nicotine stimulates gated ion channels
  receptors in the cell membrance (activates Nn
  receptors in the cell membrane) This will
  activate Na/K channel
• ? Na influx
• ?increase intracellular Na
• ? rapid depolarization and action potential
  (AP)
• ? intestinal smooth muscle contraction .

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• 2)Muscarinic Receptors agonist (cholinomimetic)
• -Act on muscarinic M3 recptors
• e.g. Cholinomimetic
• Ex.
• 1-Acetylcholine(Ach) and its derivative e.g.
  .Methacholine, Bethanecol,
• Carbachol.
• 2- Naturally occurring alkaloid e.g.
  Pilocarpine.

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• Mechanism of Action
• 1. Acetylcholine binds with M3R receptors ?
  activation of PLC
• ( phospholipase C) .
• 2. PLC hydrolyzes PIP2(phosphotidyl inositol
  biphosphate) into DAG and IP3 .
• DAGdiacylglycerol.
• IP3 inositol triphosphate.

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• 3. DAG activates Ca channel ? increase
  intracellular Ca .
• 4.IP3 increase Ca release from intracellular
  stores.
• 3,4 ? increase intracellular Ca ? intestinal
  smooth muscle contraction.

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Stimulant Drugs (Spasmogenic)

• B-Direct smooth muscle stimulants (Direct acting
  stimulant)
• e.g. Barium Chloride (Bacl2)
• Mechanism of Action
• BaCl2 stimulates act directly on the muscle
  fiber ? increase muscle contraction.

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Inhibitory drugs (Spasmolytics)

• A-Autonomic adrenergic stimulants
  (sympathomimetic)
• e.g. Adrenaline, Noradrenaline
• Mechanism of Action
• Adrenaline will stimulate a1 and ß 2 receptors
  in the intestinal smooth muscle
• ? inhibits tone and motility
• ? decrease intestinal contraction .

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Inhibitory drugs (Spasmolytic)

• B-Direct Inhibitory Drugs
• e.g. Mgcl2
• Papaverine
• Mechanism of Action Mgcl2
  inhibits the contraction of muscle fiber ? muscle
  relaxation .

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