Second messengers – Which of the following are considered bona fide intracellular second messengers generated downstream of receptors?

Introduction:
Second messengers are small intracellular molecules that relay and amplify signals from activated receptors to downstream targets. This question distinguishes true second messengers from the enzymes that synthesize them.

Given Data / Assumptions:

• IP3 and DAG are produced when PLC cleaves PIP2 in the membrane.
• Second messengers act inside the cell to modulate effectors.
• Enzymes like PLC catalyze formation but are not second messengers themselves.

Concept / Approach:
Upon receptor activation (often via GPCR Gq or RTKs), PLC hydrolyzes PIP2 into IP3 and DAG. IP3 diffuses to bind IP3 receptors on the endoplasmic reticulum, releasing Ca2+. DAG remains in the membrane, activating protein kinase C (PKC) and other effectors. Thus, IP3 and DAG fit the definition of second messengers; PLC does not.

Step-by-Step Solution:

Verification / Alternative check:
Biochemical assays show transient spikes of IP3 and DAG following receptor stimulation, with downstream PKC activation and Ca2+ transients—hallmarks of second messenger dynamics.

Why Other Options Are Wrong:

• Phospholipase C: an enzyme, not a diffusible signaling intermediary.
• None of these: incorrect because both IP3 and DAG qualify.

Common Pitfalls:
Labeling the catalytic generator as the messenger; the messenger is the product that moves or signals further downstream.

Final Answer:
Both (a) and (b)