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Old 12-02-2011
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Lungs Theophylline effect on bronchioles

They say theophylline increases the C AMP levels by inhibiting phospodiesterase. Now, I don't understand how that will cause bronchodilation as Beta 1 mediates bronchoconstriction via the same C AMP increase mechanism.

Request some luminary to shine some light on this.

Thanks
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Old 12-02-2011
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B1 receptors have no effect on bronchioles! Only M3 and B-2 receptors work on bronchioles.
M3 (muscarinic) activation causes bronchoconstriction via Gq protein activation which increases intracellular Ca2+ (you can look at the entire mechanism in the general pharm section of First Aid). Increased Ca2+ inside the myocytes causes contraction of bronchial muscle resulting in BRONCHOCONSTRICTION.
B-2 receptors, on the other hand, mediate bronchodilation. They work via increasing cAMP and protein kinase A (again look at the mechanism in First Aid) which phosphorylates myosin light chain kinase, which becomes INACTIVE, and is unable to phosphorylate myosin chains. Myosin is INACTIVE when dephosphorylated. So, myosin-actin contraction coupling does not take place and relaxation results--> BRONCHODILATION.
Theophilline is a drug which inhibits the enzyme phosphodiesterase responsible for breaking down cAMP. If cAMP is prevented from breaking down, B2 receptor effects on bronchioles will predominate i.e BRONCHODILATION. Therefore, it is used in the treatment of asthma.
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Old 12-02-2011
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Thanks Shah For the detailed explanation
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Pharmacology-, Physiology-, Respiratory-

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