Beta-blockers are a class of drugs that target beta-adrenergic receptors, blocking the action of epinephrine and norepinephrine. These drugs are used to treat heart conditions, hypertension, glaucoma, and migraine headaches and are also used off-label to alleviate stage fright in performers. Since the beta-adrenergic receptor is a GPCR, what intracellular event is prevented by the use of a beta-blocker?

Question

A.  a protein kinase cascade, initiated by the receptor's intracellular kinase domain
B.  release of an activated G protein subunit bound to GTP
C.  transport of the receptor-hormone complex into the cell and the nucleus, where it would regulate transcription
D.  a protein phosphatase cascade, initiated by the receptor's intracellular phosphatase domain

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What is the key concept addressed by the question?
What type of thinking is required?

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What do you already know about G protein-coupled receptors? What other information is related to the question?

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Given what you now know, what information is most likely to produce the correct answer?

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Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?

Answer 1

B.  release of an activated G protein subunit bound to GTP

Clarify Question
What is the key concept addressed by the question?
        · What intracellular event is prevented by beta-blockers?
What type of thinking is required?
            o This is an analyze question because you have to discriminate between different potential results of using a beta-blocker.

Gather Content
What do you already know about G protein-coupled receptors? What other information is related to the question?
        · G protein-coupled receptors are found in the cell membrane and ligands outside of the cell bind to the receptors to activate G proteins located inside the cell. When activated, G proteins bind to GTP and are released from the receptor. These G proteins in turn activate second-messenger producing enzymes to elicit changes within the cell. Such receptors are important for hydrophilic molecules such as protein hormones which cannot cross the phospholipid bilayer of the cell membrane.

Choose Answer
Given what you now know, what information is most likely to produce the correct answer?
       · Let us examine the answers. One of the answers suggests that the drug would need to get into the cell’s nucleus where it would regulate transcription. While hydrophobic molecules like steroid hormones can diffuse across the cell membrane and into the cell’s nucleus to elicit changes in gene expression, protein hormones cannot do this and so must use receptors located on the outside of the cell. G protein-coupled receptors bind to a variety of unique ligands, so can be involved in a number of different cellular pathways. G proteins are indeed proteins. They are enzymes that bind to GTP when active and hydrolyze it to GDP. Activated G protein activates channels or enzymes that produce second messengers likecAMP or IP3. Receptors that activate intracellular kinase domains act on the amino acids serine, threonine, and tyrosine. One of the most common is receptor tyrosine kinases (RTKs). Phosphatases remove phosphates instead of add them like kinases. Phosphatases are usually not associated with receptors.

Reflect on Process
Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        · Answering this question correctly depended upon analyzing each potential answer for accuracy in terms of describing the role of G protein-coupled receptors. If you got the answers correct, great! If not, which answers did you choose? Did you think that G-proteins cross the nuclear membrane? Because proteins are usually hydrophilic, they do not readily cross membranes. Did you know that G proteins are associated with GTP, so you selected that answer? You were correct! G proteins do hydrolyze GTP to GDP, acting like an on-off switch, but it is a protein. If you selected one of the answers referring to intracellular kinase domains and phosphatase domains, they were referring to different types of receptors/enzymes and not G protein-coupled receptors.