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Biochemistry · Cyclic nucleotides: sildenafil
Sample itemA man with erectile dysfunction takes sildenafil. Which nucleotide-related mechanism produces smooth muscle relaxation?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. Inhibition of phosphodiesterase 5, which prevents breakdown of cGMP generated after nitric oxide activates guanylyl cyclase
Nitric oxide from nerve terminals and endothelium activates soluble guanylyl cyclase to produce cGMP, which relaxes vascular smooth muscle in the corpus cavernosum. PDE5 hydrolyses cGMP; sildenafil inhibits it and so prolongs the effect. Concurrent nitrates are contraindicated because of profound hypotension, and PDE6 cross-inhibition can give visual disturbance.
Option by option
A. Inhibition of guanylyl cyclase, which lowers cGMP
Inhibiting guanylyl cyclase would reduce cGMP and cause vasoconstriction.
B. Release of calcium from the sarcoplasmic reticulum through IP3
IP3-mediated calcium release produces contraction rather than relaxation.
C. Activation of adenylyl cyclase, which raises cAMP
Raising cAMP is the effect of agents like beta-agonists and forskolin, not sildenafil.
D. Inhibition of phosphodiesterase 5, which prevents breakdown of cGMP generated after nitric oxide activates guanylyl cyclase (correct)
Preventing cGMP degradation amplifies the nitric oxide signal and sustains relaxation.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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