What is a second messenger?

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From the Guidelines

A second messenger is a molecule that relays signals from receptors on the cell surface to target molecules inside the cell, such as cyclic guanosine monophosphate (cGMP) or reactive oxygen species (ROS).

Characteristics of Second Messengers

  • They are intracellular signaling molecules that transmit signals from receptors on the cell surface to target molecules inside the cell
  • They can be produced in response to a variety of stimuli, including hormones, neurotransmitters, and environmental stressors
  • They play a crucial role in regulating various cellular processes, including metabolism, gene expression, and cell growth and differentiation

Examples of Second Messengers

  • cGMP: a key second messenger involved in the regulation of vascular smooth muscle tone and platelet activation, as seen in the context of B-type natriuretic peptide signaling 1
  • ROS: a group of reactive molecules that can function as second messengers, regulating redox-dependent signaling pathways and playing a role in oxidative stress and cell damage 1
  • cyclic adenosine monophosphate (cAMP): a second messenger involved in the regulation of various cellular processes, including metabolism and gene expression

Regulation of Second Messengers

  • Second messengers can be produced through the activation of specific enzymes, such as guanylyl cyclase or adenylyl cyclase
  • They can be regulated by feedback mechanisms, such as degradation or inhibition of production, to prevent excessive signaling
  • They can interact with specific target molecules, such as protein kinases or phosphodiesterases, to regulate downstream signaling pathways For example, adenosine interacts with purinergic subclass A2 receptors to increase cytosolic cAMP as the second messenger for vasorelaxation 1.

From the Research

Definition of Second Messengers

  • Second messengers are small molecules and ions that relay signals received by cell-surface receptors to effector proteins 2
  • They include a wide variety of chemical species, such as hydrophobic molecules (e.g., lipids and lipid derivatives), polar molecules (e.g., nucleotides and ions), gases, and free radicals 2
  • Second messengers are typically present at low concentrations in resting cells and can be rapidly produced or released when cells are stimulated 2

Characteristics of Second Messengers

  • They have diverse properties that allow them to signal within membranes, within the cytosol, or between the two 2
  • The levels of second messengers are exquisitely controlled temporally and spatially 2
  • Second messengers can be highly amplified during signaling through enzymatic reactions or opening of ion channels 2
  • They can diffuse rapidly from the source and bind to target proteins to alter their properties (activity, localization, stability, etc.) and propagate signaling 2

Examples of Second Messengers

  • Calcium ion (Ca(2+)) plays an important role in stimulus-response reactions of cells as a second messenger 3
  • Nucleotide second messengers, such as cAMP, cGMP, and c-di-GMP, act as intracellular 'secondary' signals that represent environmental or cellular cues 4
  • Cyclic nucleotides, such as cAMP and cGMP, help in the coordination of cellular functions, mainly through their stimulatory effect on multisubstrate protein kinases 5

Signaling Pathways

  • Second messengers can operate in local signaling pathways that can act in parallel without cross-talking 4
  • Signaling pathways operating with different nucleotides can intersect in elaborate signaling networks 4
  • Second messengers can play conserved general roles, such as coordinating growth and survival in response to nutrient availability and various stresses 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Second Messengers.

Cold Spring Harbor perspectives in biology, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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