How does caffeine ingestion lead to heightened alertness and sleeplessness if it blocks the activity of cAMP?

Epinephrine starts a signal transduction pathway that produces cAMP and leads to the breakdown of glycogen to glucose, a major energy source for cells. But glycogen breakdown is actually only part of a “fight-or-flight response” that epinephrine brings about; the overall effect on the body includes increased heart rate and alertness, as well as a burst of energy. If caffeine blocks the activity of cAMP phosphodiesterase, how would caffeine ingestion lead to heightened alertness and sleeplessness.

First of all, you are oversimplifying the cascade of events. But having said that, even if we follow your reasoning, blocking phosphodiesterase will lead to more cAMP, and thus, heightened alertness, and sleeplesness. So, caffeine and other methylxanthines, don’t block cAMP, they block cAMP metabolism.

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