1. 313PHL Lab #4 Identification of effect and site of action of an unknown drug using isolated guinea-pig ileum

2. Guinea pig ileum is a smooth muscle receive dual nerve supply from autonomic nervous system (sympathetic and parasympathetic) .
Parasympathetic tone is dominant in ileum which Ach cause contraction by stimulating M3-R .

3. Why Guinea pig ileum is used?
No myogenic contraction so any drug induce contraction can be seen.
Very sensitive to histamine unlike the rabbit due to the presence of histaminase enzyme.

4. Types of receptors present in guinea-pig ileum
Cholinergic receptors .
Serotonergic or tryptaminergic receptors (5-HT1→5-HT7) .
Histaminergic receptors .
Adrenergic receptors .

5. Types of receptors in guinea-pig ileum:
1- Cholinergic receptors:
Receptor
Agonist
Antagonist
nicotinic neuronal receptor (Nn- R)
Dil. Nicotine
Conc. Nicotine
muscarinic receptor(M3 -R)
Ach
Atropine

6. Types of receptors in guinea-pig ileum:
2-Serotonergic or tryptaminergic (5-HT )receptors :
Serotonin = 5-HT(5-hydroxytryptamine) .
5-HT2A receptor found in smooth muscle and bronchi .
Receptor
Agonist
Antagonist
5-HT2A
serotonin
-Methysergide & ketanserin (selective) .
-cyproheptadine (non selective block both H &5-HT receptors) .

7. Types of receptors in guinea-pig ileum:
3- Histaminergic receptors:
Histamine is an autacoids naturally occurring in the body .
Receptor
distribution
Action
Agonist
Antagonist H1
Smooth muscles
contraction
Histamine
Mepyramine
cyproheptadine H2
Gastric mucosa
Gastric acid secretion
Cimetidine
Ranitidine H3
Presynaptic
Decrease release of Histamine
Thioperamide

8. Types of receptors in guinea-pig ileum:
4- Adrenergic receptors:
Receptor
Agonist
Antagonist α1
Adrenaline
phentolamine
ß 2 -

9. Types of drugs act on guinea-pig ileum : Spasmogens:
1- Cholinergic stimulants , e.g. Ach .
MOA :
2- Histaminergic stimulants, e.g. Histamine .
MOA:
histamine act on H1 R which coupled with Gαq → stimulate PLC
→ Hydrolysis of (PIP2) into:
1- DAG → ↑opening of Ca+2 channels
2- IP3 → mobilization of Ca+2 from its stores
1&2 → ↑ intracellular Ca+2
→ Contraction .

10. Spasmogens: 3- Serotonergic stimulants . e.g. Serotonin.
4- Direct acting stimulants (spasmogens) .
e.g. Barium chloride, Calcium chloride .

11. Spasmolytics :
1- Direct acting Spasmolytics .
e.g. Mgcl2
Papaverine

12. Experiment Identification of effect and site of action of an unknown drug using isolated guinea-pig ileum  
Blocker +
Agonist
Unknown
Unknown
Agonist