Question
A 61-year-old man comes to the physician because of a 1-year history of increased urinary frequency, weak urinary stream, and occasional straining to void urine. Rectal examination shows a large, nontender prostate without asymmetry or nodularity. His serum creatinine, prostate-specific antigen, and urinalysis are all within the reference range. A diagnosis of benign prostatic hyperplasia is made, and treatment with tamsulosin is begun. Which of the following changes in intracellular messaging is most likely to occur in response to this drug?
| A. |
Decreased activity of protein kinase A
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| B. |
Increased production of diacylglycerol
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| C. |
Increased activity of protein kinase C
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| D. |
Decreased activity of phospholipase C
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Show Answer
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Correct Answer � D
Explanation
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Ans-D-Decreased activity of phospholipase C
Decreased activity of protein kinase A
Protein kinase A (PKA) is involved in the Gs and Gi GPCR pathways. Activation of Gs protein ultimately leads to activation of protein kinase A. Activation of Gi protein, in contrast, ultimately decreases the activity of protein kinase A. However, tamsulosin is an inhibitor of the alpha-1 receptor, which is not a Gs or Gi GPCR, and would therefore not be expected to affect protein kinase A activity.
Additional Information
Beta-1 receptors, beta-2 receptors, and beta-3 receptors function via activation of Gs and Gi proteins.
Increased production of diacylglycerol
Diacylglycerol (DAG) is a second messenger in the GPCR pathway of the alpha-1 receptor, among others. Activation of the alpha-1 receptor results in increased production of DAG. Since tamsulosin is an alpha-1 receptor inhibitor, DAG production via this pathway would be expected to decrease rather than increase here.
Increased activity of protein kinase C
Protein kinase C (PKC) is involved in intracellular signaling in the GPCR pathway of the alpha-1 receptor, among others. Activation of the alpha-1 receptor activates a Gq protein, which ultimately results in activation of PKC. Since tamsulosin is an alpha-1 receptor inhibitor, PKC activity via this pathway would actually be expected to decrease rather than increase in this scenario.
Decreased activity of phospholipase C
Phospholipase C is an effector molecule which is activated by a Gq protein-coupled receptor (GPCR), as exemplified here in the signaling pathway of the alpha-1 receptor. Activation of the alpha-1 receptor activates a Gq protein, which in turn activates the effector molecule phospholipase C. Phospholipase C then cleaves the membrane-bound phospholipid PIP2 into the second messengers IP3 and DAG, which activate protein kinase C. Because tamsulosin antagonizes the function of alpha-1 receptors, decreased activity of phospholipase C will result.
