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You are a graduate student working with isolated aortic rings in a muscle bath. You measure vessel contraction (force in mN) in response to compounds that are thought to bind to G protein coupled receptors. When you expose aortic rings to drug X alone you get no response. When you expose the aorta to drug Y alone the vessel contracts generating a force of 17mN. When you expose the aorta to drugs X and Y together the aorta contracts more than with drug Y alone and generates a force of 24mN.

Where on the receptor does drug X bind?

Where on the receptor does drug Y bind?

Explain why drugs X and Y have an additive effect.

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Answer:

Explanation:

a) Drug X binds to the secondary site or co-agonist site of the receptor since it has no effect on contraction.

b) Drug Y binds to the primary site or agonist site of the receptor since it elicits contraction when aorta is exposed to it.  

c) Drugs X and Y have a synergistic effect because the sum of their forces measured independently is larger than when they are tested simultaneously.