2021 BIOM2402 Virtual Ileum Practical Report PDF

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Virtual ileum report...

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2021 BIOM2402 VIRTUAL ILEUM PRACTICAL REPORT Student name: Senthuran Sundarakumar Student number: 46471457

Note that the legend and formatting for tables are already set up for you. You will need to include your own legend and key on all of your figures (these will be worth marks). Introduction to agonists, antagonists, potency and efficacy: An agonist is a substance that binds to a receptor to then induce a biological response. Once bound, the agonist causes the activation of second messengers to trigger the receptor-mediated biological response. Antagonists are substances that work to oppose the biological responses triggered by the agonist. This is done so through the interaction with receptors and via drugs or proteins. When the potency of such drugs is mentioned, it means the concentration of the drug required to produce 50% of the drugs maximal response and this value is known as the EC50 of the drug. The efficacy of a drug regards the drugs likelihood to produce a physiological response by triggering a receptor. The efficacy of a drug can be measured by looking at and measuring the physiological response induced i.e. contractile force of tissue.

Mark: _____ / 0.4

Table 1: EC50 values for each agonist drug. EC50 values are given in ________(µm)_______ (units). *represents the agonist that exerts the strongest maximal contraction against ileum tissue. These must me manually calculated units from hand-drawn graphs and NOT in notation format.

Agonist 1 EC50

0.042

Agonist 2 0.89

Agonist 3 3.4

Mark: ___ / 0.8

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Figure 1:

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Attach Figure 1 (plotted on semi-log graph paper) on a separate sheet of paper and attach here. Scan this image to include in your Turnitin submission.

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Key: Blue Line (Leftmost curve): Acetylcholine Red Line (Centre curve): Carbachol Black Line (Rightmost curve): Furmethide

Mark: ____ / 2.2

Figure 2:

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Mark: ___ / 1.8 Results and discussion for agonist curves and data: From the graph and table, we can see that the EC50 values for acetylcholine, carbachol and furmethide are 0.042 µm, 0.89 µm and 3.4 µm respectively. Potency can be determined from these values as potency has an inversely proportional relationship with EC50 and so it can be seen that of the three, acetylcholine is the most potent drug and furmethide is the least potent drug. The efficacy of a drug can be found by comparing the maximum EMax value of the curve after normalising it to a specific drug. In this case, as shown above in figure 2, it was normalised to acetylcholine and both acetylcholine and carbachol both reach values of 100% whereas furmethide only gets to ~45%. From this we can see that acetylcholine and carbachol have the highest efficacy and furmethide has the lowest. From figure 2 we can see that of the three agonists tested only acetylcholine and carbachol are full agonists due to them being able to achieve the 100% for maximum contractile response from the rat ileum tissue. Furmethide is thus a partial agonist due to only having a 45% maximum contractile response. The ileum is located within the gastrointestinal tract and so it is likely the receptors that the drugs are interacting with are muscarinic receptors. This explains the percentage Emax trends in figure 2 as muscarinic receptors are G-protein coupled receptors and so produce a greater response via second messengers when acetylcholine and carbachol are bound than when compared to furmethide.

Mark: ___ / 0.9

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Figure 3:

Mark: ___ / 2.0

Table 2: EC50 values of agonist alone and in the presence of 3 different concentrations of reversible competitive antagonist (Cetirizine) (antagonist name). EC50 values are given in ________(µm)_______ (units). 0 nM

Antagonist concentration 0.46

1 nM 1.26

10 nM 18.89

100 nM 72.14

EC50

Mark: ___ / 1.0

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Results and discussion for agonist in the presence of antagonist data: Figure 3 shows that the EC50 values are different between different concentrations of cetirizine. We can also see that the percentage Emax value remains constant and EC50 changes which shows that the antagonist displays reversible competitive antagonism. This is further backed by the fact that the agonist only solution has a lower EC50 of 0.46µm than the other solutions which had values of 1.26 µm, 18.89 µm and 72.14 µm. This is because the available number of receptors decrease and there is a need for more histamine as “competition” for the receptors. Histamine binds with the different histamine receptors i.e., H1, H2, H3 and H4 receptors which are all Gprotein coupled receptors. Cetirizine is a known antihistamine which poses as competition for these H receptors, and in the case of the rat ileum, specifically the H1 receptor.

Mark: ___ / 0.9

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