Difference Between Neuropeptides and Neurotransmitters

Main Difference – Neuropeptides vs Neurotransmitters

Neuropeptides and neurotransmitters are chemical substances which act as mediators for the transmission of impulse from one neuron to another neuron through the synapse. Both neuropeptides and neurotransmitters are polypeptide derivatives. The transmission of neuron signal across the synapse occurs in several steps. First, the neurotransmitter is released from the presynaptic neuron into the synapse. Then, the neurotransmitter diffuses across the synaptic cleft and binds to specific receptors. Neuropeptides are a type of neurotransmitters. Neuropeptides are large molecules but neurotransmitters are small molecules. The main difference between neuropeptides and neurotransmitters is that neuropeptides are slow-acting and produce a prolonged action whereas neurotransmitters are fast-acting and produce a short-term response.

This article looks at,

1. What are Neuropeptides
      – Definition, Characteristics, Function
2. What are Neurotransmitters
     – Definition, Categorization, Characteristics, Function
3. What is the difference between Neuropeptides and Neurotransmitters

Difference Between Neuropeptides and Neurotransmitters - Comparison Summary

What are Neuropeptides

Neuropeptides are neurotransmitters made up of amino acids, each connected by peptide bonds. They are relatively large and are composed of 3 to 36 amino acids. They are released into the synaptic cleft along with another neurotransmitter. Neuropeptides are derived from about 90 amino acids large, inactive precursors. The removal of the signal sequence from the neuropeptide precursor produces the bioactive peptide. In some neuropeptide precursor peptides, the same bioactive neuropeptide occurs in multiple copies. Neuropeptides are synthesized in the cell body of the neuron. Then, they are sequestrated within the lumen and transported to the axon, while undergoing its processing events like signal peptide cleavage. The bioactive neuropeptides are stored in large dense-core vesicles (LDCVs). After the exocytosis of LDCVs, the membrane components of LDCVs are reinternalized. Therefore, no re-use of neuropeptides occurs in the synapse. The release of neuropeptides occurs at low cytosolic Ca2+ concentrations. But, Ca2+ ions usually stimulate the exocytosis of LDCVs. Thus, Ca2+ ions from other sources like internal stores or transmembrane current may be used for exocytosis. The synthesis of neuropeptides is shown in figure 1.

Difference Between Neuropeptides and Neurotransmitters

Figure 1: Neuropeptide synthesis

Table 1: Origins of Neuropeptides and Examples



Hypothalamic Releasing Hormones

TRH, LHRH, GHIH (Somatostatin)

Pituitary Peptides

ACTH, β-Endorphin, α-MSH, PRL, LH, TSH, GH, Vasopressin, Oxytocin

Peptides Acting on Gut & Brain

Leucin enkephalin, Methionine enkephalin, Subs P, Gastrin, CCK, VIP, Nerve GF, Brain derived neurotropic factors, Neurotrensin, Insulin, Glucagon

From other Tissues

Ag-II, Bradykinin, Carnosine, Sleep peptides, Calcitonin

What are Neurotransmitters

Neurotransmitters are chemicals which transmit signals from a neuron to a target cell across a synapse. They are stored in synaptic vesicles, which are present at the terminal of the presynaptic neuron cells. Once the presynaptic neuron is stimulated by a nerve impulse, neurotransmitters are released into the synapse from the axon terminal. The released neurotransmitters diffuse across the synapse and bind to the specific receptors on the postsynaptic neuron. Hence, neurotransmitters are in the direct apposition to their target cells.

Categorization of Neurotransmitters

Neurotransmitters are categorized into types based on the function; they are excitatory and inhibitory neurotransmitters. Excitatory neurotransmitters increase the trans-membrane ion flow, allowing the postsynaptic neuron to produce an action potential. In contrast, inhibitory neurotransmitters decrease the trans-membrane ion flow, prohibiting the postsynaptic neuron to produce an action potential. However, the overall effect of excitatory and inhibitory functions determines whether the postsynaptic neuron “fires” or not.

Acetylcholine, biogenic ammines, and amino acids are the three classes of neurotransmitters. Acetyl and choline are involved in the production of acetylcholine, which acts on the neuromuscular junctions. Biogenic amines found in the brain are involved in the emotional behavior of the animal. They include catecholamines like dopamine, epinephrine, and norepinephrine (NE) and indolamines like serotonin and histamine. They also help to regulate the biological clock. The function of biogenic amines depends on the type of receptor they bind to. Glutamate and gamma-aminobutyric acid (GABA) are amino acid neurotransmitters. Glutamates act on the brain. Neuropeptides like endorphins and Substance P are strings of amino acids, which mediate pain signals. A synapse with neurotransmitters is shown in figure 2.

Main Difference -Neuropeptides vsNeurotransmitters

Figure 2: A Synapse

Difference Between Neuropeptides and Neurotransmitters


Neuropeptides: Neuropeptides are short chains of amino acids which serve as neurotransmitters.

Neurotransmitters: Neurotransmitters are chemical substances which are released at the end of a nerve cell by the arrival of a nerve impulse, transmitting the impulse into another neuron, muscle or some other structure.

Molecular Weight

Neuropeptides: Neuropeptides have high molecular weight.

Neurotransmitters: Neurotransmitters have low molecular weight.


Neuropeptides: Neuropeptides are slow-acting.

Neurotransmitters: Neurotransmitters are fast-acting.


Neuropeptides: Neuropeptides produce a slow response.

Neurotransmitters: Neurotransmitters produce acute response.


Neuropeptides: Neuropeptides produce a prolonged action.

Neurotransmitters: Neurotransmitters trigger short-term response.

Receptor Proteins

Neuropeptides: Neuropeptides act on a number of receptor proteins.

Neurotransmitters: Most of the neurotransmitters only act on a specific receptor.

Metabolic Machinery

Neuropeptides: Neuropeptides change metabolic machinery.

Neurotransmitters: Most of the neurotransmitters do not change the metabolic machinery.


Neuropeptides: Neuropeptides alter the expression of specific genes.

Neurotransmitters: Most of the neurotransmitters do not alter gene expression.


Neuropeptides: Neuropeptides are synthesized in rough endoplasmic reticulum and Golgi apparatus.

Neurotransmitters: Neurotransmitters are synthesized in the cytosol of presynaptic neuron terminals.


Neuropeptides: Neuropeptides are synthesized in low concentrations.

Neurotransmitters: Neurotransmitters are synthesized in high concentrations.


Neuropeptides: Neuropeptides are found all over the neuron.

Neurotransmitters: Neurotransmitters are only found in the axon terminals of presynaptic neurons.

Stored in

Neuropeptides: Neuropeptides are stored in large dense-core vesicles (LDCVs).

Neurotransmitters: Neurotransmitters are stored in small secretory vesicles (SSVs).


Neuropeptides: Axonal streaming of neurotransmitters occurs in few cm/day.

Neurotransmitters: Neurotransmitters are released within few milliseconds upon an arrival of an action potential.

Released with

Neuropeptides: Neuropeptides are released to the synaptic cleft along with another neurotransmitter.

Neurotransmitters: Neurotransmitters are released individually depending on the action potential.

Cytosolic Ca2+ Concentration

Neuropeptides: Neuropeptides are released at low cytosolic Ca2+ concentrations.

Neurotransmitters: Neurotransmitters are released at high cytosolic Ca2+ concentrations.

Site of Action

Neuropeptides: Neuropeptides have a different site of action than their origin.

Neurotransmitters: Neurotransmitters are released in direct apposition to their target cells.


Neuropeptides: Vesicles are autolysed without reusing. Once released, they do not undergo reuptake. 

Neurotransmitters: Neurotransmitters are either destroyed by enzymes in the synaptic cleft or are reuptake by presynaptic terminal or neuroglia by active transport.


Neuropeptides: Neuropeptides are 1000 times potent than neurotransmitters.

Neurotransmitters: Neurotransmitters are less potent when compared to neuropeptides.


Neuropeptides: Oxytocin, vasopressin, TSH, LH, GH, insulin, and Glucagon are neuropeptides.

Neurotransmitters: Acetylcholine, Dopamine, Serotonin, and Histamine are neurotransmitters.


Neuropeptides and neurotransmitters are chemical mediators, which are involved in the transmission of neuron impulses. Neuropeptides are a type of neurotransmitters. Neuropeptides are short-chain amino acids and neurotransmitters are polypeptide molecules. The production of neuropeptides occurs in the cell body of the neuron while the production of neurotransmitters occurs at the axon terminal of presynaptic neurons. Neuropeptides are released at a distinct site to the site of action. Therefore, their diffusion to the active site takes time, making neuropeptides to act slowly. But they produce a prolonged response. In contrast, neurotransmitters are released directly apposition to their target, producing an acute response. Since neurotransmitters are destroyed at the presynaptic cleft, their response lasts for a short time period. Therefore, the main difference between neuropeptides and neurotransmitters is in their mechanism of action after releasing.

1.”What are Neurotransmitters?” Neurogistics. N.p., n.d. Web. 29 May 2017. <http://www.neurogistics.com/the-science/what-are-neurotransmitters>.
2.”Types of Neurotransmitters by Function – Boundless Open Textbook.” Boundless. N.p., 29 Sept. 2016. Web. 29 May 2017. <https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology-textbook/overview-of-the-nervous-system-11/neurophysiology-113/types-of-neurotransmitters-by-function-619-3349/>.
3.”Synaptic Transmitters- Neurotransmitters & Neuropeptides.” HowMed. N.p., 18 May 2011. Web. 30 May 2017. <http://howmed.net/physiology/synaptic-transmitters/>.
4. Mains, R. E., Eipper, B. A., “The Neuropeptides.” Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. U.S. National Library of Medicine, 01 Jan. 1999. Web. 30 May 2017. <https://www.ncbi.nlm.nih.gov/books/NBK28247/>.

Image Courtesy:
1. “Neuropeptide synthesis” By Pancrat – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “1225 Chemical Synapse” By OpenStax –  (CC BY 4.0) via Commons Wikimedia

About the Author: Lakna

Lakna, a graduate in Molecular Biology and Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things. She has a keen interest in writing articles regarding science.

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