Difference Between First and Second Messenger System

The key difference between first and second messenger system is that first messenger system refers to the extracellular signalling molecules while second messenger system refers to the intracellular signalling molecules.

First and second messenger systems comprise of various types of signalling molecules. First messengers are extracellular molecules, often hormones or neurotransmitters. In contrast, second messengers are intracellular molecules that transmit signals from cell membrane receptors to targets within the cell. The cell signalling process initiates when the signalling molecule (ligand) binds with the receptor of a cell. This binding changes the intracellular domain of the receptor, which triggers intracellular signalling pathways.

CONTENTS

1. Overview and Key Difference
2. What is First Messenger System
3. What is Second Messenger System
4. Similarities Between First and Second Messenger System
5. Side by Side Comparison – First vs Second Messenger System in Tabular Form
6. Summary

What is First Messenger System?

First messengers are extracellular signalling molecules. They are also called ligands. They bind with receptors located on the surface of the cells. Therefore, first messengers are extracellular substances that are unable to cross the cell membranes. But, once they bind with their respective receptors, they are able to initiate intracellular activities or initiate changes within the cell. Generally, the first messengers are very diverse. They can be environmental factors, hormones or neurotransmitters. Moreover, they can be peptides or proteins.

In order to receive signals from first messengers, there are receptors such as ion channels, intracellular receptors, G-protein coupled receptors and single-pass transmembrane receptors. First messengers help organisms to receive information from the outside world. Moreover, first messengers facilitate the communication between cells.

What is Second Messenger System?

Second messengers are intracellular molecules that send signals from receptors to targets. The cell releases second messengers in response to exposure to extracellular signalling molecules, which are first messengers. Second messengers trigger physiological processes of the cell. Such processes are cell proliferation, differentiation, migration, survival, apoptosis, muscle contraction, fertilization, and neurotransmitter release, etc.

There are several different second messenger systems within the cell. Cyclic AMP, cyclic GMP, inositol trisphosphate, diacylglycerol, and calcium are several examples. Generally, second messengers are non-protein small molecules which are made from phospholipids. They are produced after the first messenger dependent receptor activation. Moreover, second messenger molecules are typically small molecules that can easily diffuse within the cell. They operate through the activation of protein kinases. In fact, each second messenger associates a particular type of protein kinase. Sometimes, second messengers couple with multi-cyclic kinases and amplify the strength of the original signal.

What are the Similarities Between First and Second Messenger System?

• First and second messenger systems comprise of signalling molecules.
• They can be classified as juxtacrine, paracrine, and endocrine depending on the range of the signal.
• Second messengers are produced after the first messenger-dependant receptor activation.

What is the Difference Between First and Second Messenger System?

First messengers are the extracellular substances that can initiate intracellular activities while second messengers are the intracellular signalling molecules that send signals from receptors to targets within the cell. So, this is the key difference between first and second messenger system. First messengers are found outside the cell while second messengers are found inside the cell.

Furthermore, the first messengers work through the binding with their respective receptors while second messengers work through the activation of respective protein kinases. Thus, this is another difference between first and second messenger system. Besides, the first messengers are different types including hormones, neurotransmitters, local mediators, etc., while second messengers small molecules such as cAMP system, phosphoinositol system, cGMP System, Tyrosine kinase system and arachidonic acid system, etc.

Below infographic tabulates the differences between first and second messenger system.

Summary – First vs Second Messenger System

First and second messenger systems are signalling molecules participating in cell communication systems. First messengers are extracellular signalling molecules while second messengers are intracellular signalling molecules. First messengers bind with cell receptors and initiate intracellular activities. Second messengers receive signals from receptors and sent to targets. Moreover, first messengers can be environmental factors, hormones, neurotransmitters, etc. while second messengers are small non-protein molecules such as cAMP, cyclic guanosine monophosphate (cGMP), diacylglycerol (DAG), inositol trisphosphate (IP3), and Ca²⁺ ions, etc. Thus, this is the summary of the difference between first and second messenger system.

Reference:

1. “Signal Transduction Pathway | Cell Signaling (Article) | Khan Academy”. Khan Academy, 2020, Available here.
2. Kodis, Erin & Smindak, Richard & Kefauver, Jennifer & Heffner, Danielle & Aschenbach, Krista & Brennan, Elliot & Chan, Kelvin & Gamage, Kanchana & Lambeth, Philip & Lawler, Jessica & Sikora, Arthur & Vercruysse, Nicholas & Deppmann, Christopher. (2012). First Messengers. 10.1002/9780470015902.a0024167.

Image Courtesy:

1. “Signal transduction pathways” By cybertory – This file was derived from:  Signal transduction v1.png (CC BY-SA 3.0) via Commons Wikimedia
2. “Second Messenger Mechanism” By Lunska at English Wikipedia – Own work (Public Domain) via Commons Wikimedia