Morphine binds to u-opioid receptors that are also coupled to G proteins. Addict

Question

Morphine binds to u-opioid receptors that are also coupled to G proteins. Addiction of morphine leads to a tolerance phenomenon in which the pain killing effects of the drug become less effective. It has been found recently that mice that lack the gene coding for -Arrestin-2 do not show this tolerance. What is -arrestin and show the events that lead to its regulation G-protein coupled receptor activity. Why is this tolerance phenomenon absent in these mice? Describe an experiment to test your explanation.

Explanation / Answer

-arrestin is intracellular protein which is crucial in signal transduction. When the G-protein coupled receptor binds to -arrestin it prevents G-protein coupling and other protein bind which leads to activation of extracellular regulated kinase or endocytosis. Which is an important mechanism in desensitization.

Since the  -Arrestin-2 gene is not present in the mice, it does not undergo this reaction and hence this tolerance phenomenon is absent in this mice.

To test the explanation mice cell lines can be cloned with the  -Arrestin-2 gene and can test the tolerance towards it. And the pathway analysis can be done to see the effect.

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