A researcher finds that a novel drug blocks the action of phosphodiesterase-5 (PDE5) in vascular smooth muscle. The resulting clinical effect is vasodilation. The biochemical mechanism is:

• A Increased cGMP activates PKG, which phosphorylates and inactivates myosin light chain kinase, causing relaxation ✓
• B Increased cAMP activates PKA, which phosphorylates myosin light chain kinase, causing relaxation
• C Increased cGMP directly opens calcium channels, causing muscle contraction
• D Decreased cAMP reduces PKA activity, lowering intracellular calcium

Explanation

PDE5 degrades cGMP; its inhibition raises cGMP levels in smooth muscle. Elevated cGMP activates protein kinase G (PKG), which phosphorylates myosin light chain kinase (MLCK) at an inhibitory site, reducing its activity. With less active MLCK, myosin light chains remain unphosphorylated and smooth muscle relaxes — the mechanism underlying sildenafil's vasodilatory and erectile effects. cAMP/PKA is a separate vasodilatory pathway used by prostacyclin.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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