1. You are examining the cellular response to a new drug. You treat cells with t

Question

1. You are examining the cellular response to a new drug. You treat cells with the drug and measure the intracellular levels of cAMP and find that they increase as a response to the treatment.

With what type of receptor would you predict the drug interacts and give an example of how is the rise in intracellular cAMP used to change cellular physiology or metabolism (i.e. blood sugar level)?


2. G protein-coupled receptors activate G proteins by reducing the strength of GDP binding.
This results in rapid dissociation of bound GDP, which is then replaced by GTP, which is present in the cytosol in much higher concentrations than GDP. What consequences would result from a mutation in the a subunit of a G protein that caused its affinity for GDP to be reduced without significantly changing its affinity for GTP[i.e., GDP is unable to bind]?

Explanation / Answer

1. The increase in intracellular cAMP concentration is a classical response of a few kinds of 2nd messenger pathways. These begin with a receptor whose activation causes the activation of a G-coupled protein. The G-protein binds a transducer such as adenylate cyclase, which causes the production of cAMP. cAMP is a 2nd messenger which either facilitates direct protein activation or translation AND/OR activates the transcription process for specific proteins. Usually protein kinase activation ---> other proteins --> more transcription. In summary:

receptor activated --> G-protein activated --> adenylate cyclase turns on --> make cAMP --> activate protein kinases --> turn on other proteins --> effect is to activate hormone secretion, open ion channel, turn on specific transcription, etc.

A few examples of these:
-response to insulin in skeletal muscle cells causes activation of glucose intake pathways
-antigen/antibody complex binding to an appropriate receptor on immune system cells activates cytokine production, antibody production, receptor upregulation to more easily sense the same antigen, etc.
-SA (sinoatrial) node in the heart, which sets the pace of the heartbeat, responds to neurotransmitter stimulus from the brain using a 2nd messenger system in order to cause nerve impulses which will make the entire heart beat in an orderly fashion
-control over mitosis progression

2. As you said, G-proteins are activated causing less GDP binding, more GTP binding....this GTP (similar to ATP) activates production of cAMP to set off a 2nd messenger cascade. This is normally regulated very tightly because active cAMP has very powerful effects such as mitotic regulation. If GDP binding were not possible, GTP binding would more freely occur. The target of GTP would be activated more often, resulting in a much higher rate of cAMP production. Any of the examples above would be affected, implicating several diseases including progression of rapid mitosis that could become carcinogenic.

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