1. Effect of Certain Agonists & Antagonists on Isolated Guinea-pig Ileum
Lab #4

2. Objectives Discuss the types of receptor present in guinea-pig ileum
Explain the action of agonists & their specific antagonists
Discuss the reasons for using guinea-pig ileum
Explain of effect of different drugs on isolated guinea-pig ileum curve

3. Types of receptors in GPI
1- Cholinergic receptors
2- Serotonergic or tryptaminergic receptors (5-HT1→5-HT7)
3- Histaminergic receptors

4. Cholinergic receptors
1- NN R
Agonist: Dil. Nicotine
Antagonist: Conc. Nicotine
2- M3 R
Agonist: Ach
Antagonist: Atropine

5. Serotonergic or tryptaminergic receptors
Serotonin = 5-HT(5-hydroxytryptamine)
5-HT receptors in GPI:
5-HT2A
Agonist: serotonin
Antagonist: ketanserin
methysergide
cyproheptadine (blocks 5-HT2A & H1)

6. Histaminergic receptors
R subtype
Distribution
Action
Agonist
Antagonist H1
Smooth muscles
contraction
Histamine
Mepyramine
cyproheptadine H2
Gastric mucosa
Gastric acid secretion
Cimetidine
Ranitidine H3
Presynaptic
Autoregulation of H release
Thioperamide
N.B. Histamine acts by stimulating Gs protein → ↑ cAMP → ↑ [Calcium]ic → contraction

7. e.g. Barium chloride e.g. Papaverine Direct acting drugs
Direct spasmogen
e.g. Barium chloride
Direct spasmolytic
e.g. Papaverine

8. Advantages of GPI
No myogenic contraction
More sensitive to histamine

9. Experiment N Key: Hist.=histamine AH= antihistamine 5-HT=serotonin W N
0.1ml
Bacl2
0.1ml
5-HT
Ach
0.1ml
Hist.
0.1ml
W+N
W+N
Ach 0.1ml
AH 0.2 ml
Hist. 0.1ml
Bacl2 0.1ml
Atropine 0.1ml
5-HT 0.1ml
Papaverine 0.1ml
Key:
Hist.=histamine
AH= antihistamine
5-HT=serotonin

10. Experiment
Identification of site of action of an unknown drug using isolated guinea-pig ileum N
W N
W+N
W+N
Ach
0.1ml
Hist.
0.1ml
Unk.
Unk.
Ach 0.1ml
Hist. 0.1ml
Atropine 0.1ml
AH 0.2 ml
Key:
Ach= acetylcholine
Hist.=histamine
AH= antihistamine
Unk.= unknown