Why are second messengers important?

They carry the signal from a receptor deep into the cell, amplify it because one enzyme can make many messenger molecules, and allow the response to be coordinated and quickly switched off.

How does calcium act as a signal?

Cells keep cytoplasmic calcium very low, so a controlled release from stores or entry from outside produces a sharp rise that binding proteins such as calmodulin detect to trigger responses.

Intracellular Second Messengers

Second messengers are small intracellular molecules that relay and amplify signals from activated receptors to a cell's enzymes and other targets.

Definition

A second messenger is a small intracellular signaling molecule whose concentration changes rapidly in response to receptor activation and which relays the signal to effector proteins.

Scope

This topic covers the principal second messengers, including cyclic AMP, calcium ions, and the inositol phospholipid products inositol trisphosphate and diacylglycerol, how they are produced and removed, and how they activate downstream effectors such as protein kinases.

Core questions

What makes a molecule a good second messenger?
How is cyclic AMP produced and how does it act?
How does calcium serve as a versatile intracellular signal?
How do inositol trisphosphate and diacylglycerol split a signal into two branches?

Key theories

Inositol trisphosphate and calcium signaling: Phospholipase C cleaves a membrane phospholipid into inositol trisphosphate, which releases calcium from internal stores, and diacylglycerol, which activates protein kinase C, coupling receptor activation to two intracellular branches.

Mechanisms

Activated receptors stimulate enzymes that change second-messenger levels. Adenylyl cyclase makes cyclic AMP, which activates protein kinase A; phosphodiesterases degrade it. Phospholipase C cleaves the membrane lipid PIP2 into inositol trisphosphate, which opens calcium channels on internal stores, and diacylglycerol, which activates protein kinase C. Calcium itself acts through binding proteins such as calmodulin. Because these messengers are small and diffusible, they spread and amplify signals, and their rapid removal allows quick termination.

Clinical relevance

Second messengers explain how cells convert receptor activation into fast, amplified, and spatially organized responses, a core concept across cell signaling. The treatment here is descriptive and non-prescriptive.

History

Sutherland's discovery of cyclic AMP introduced the second-messenger concept; Berridge elucidated inositol trisphosphate and calcium signaling, and Nishizuka identified protein kinase C as the diacylglycerol target, mapping the major messenger systems.

Key figures

Earl Sutherland
Michael Berridge
Yasutomi Nishizuka

Seminal works

berridge1993
alberts2014

Frequently asked questions

Why are second messengers important?: They carry the signal from a receptor deep into the cell, amplify it because one enzyme can make many messenger molecules, and allow the response to be coordinated and quickly switched off.
How does calcium act as a signal?: Cells keep cytoplasmic calcium very low, so a controlled release from stores or entry from outside produces a sharp rise that binding proteins such as calmodulin detect to trigger responses.