Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity.

Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M

Frontiers in pharmacology12 Sept 2017Cited by 31 (Europe PMC)

PMID28955242PMCIDPMC5601071DOI10.3389/fphar.2017.00643PepBankPUB-28955242

Summary

Depression is a devastating mental disorder that affects 20% of the population worldwide. Despite their proven efficacy, antidepressants present a delayed onset of action and serious adverse effects. Seven years ago, we described spadin (PE 12-28) as a promising endogenous peptide with antidepressant activity. Spadin specifically blocks the TREK-1 channel. Previously, we showed in vivo that, spadin activity disappeared beyond 7 h after administration. In order to improve in vivo spadin stability and bioavailability, we screened spadin analogs and derivatives. From the study of spadin blood degradation products, we designed a 7 amino-acid peptide, PE 22-28. In vitro studies on hTREK-1/HEK cells by using patch-clamp technique, showed that PE 22-28 displayed a better specificity and affinity for TREK-1 channel compared to spadin, IC₅₀ of 0.12 nM vs. 40-60 nM for spadin. In the same conditions, we also pointed out that different modifications of its N or C-terminal ends maintained or abolished TREK-1 channel activity without affecting PE 22-28 affinity. In vivo, the antidepressant properties of PE 22-28 and its derivatives were demonstrated in behavioral models of depression, such as the forced swimming test. Mice treated with spadin-analogs showed a significant reduction of the immobility time. Moreover, in the novelty suppressed feeding test after a 4-day sub-chronic treatment PE 22-28 reduced significantly the latency to eat the food pellet. PE 22-28 and its analogs were able to induce neurogenesis after only a 4-day treatment with a prominent effect of the G/A-PE 22-28. On mouse cortical neurons, PE 22-28 and its derivatives enhanced synaptogenesis measured by the increase of PSD-95 expression level. Finally, the action duration of PE 22-28 and its analogs was largely improved in comparison with that of spadin, up to 23 h instead of 7 h. Taken together, our results demonstrated that PE 22-28 and its derivatives represent other promising molecules that could be an alternative to spadin in the treatment of depression.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice after 4-day sub-chronic treatment, PE 22‑28 significantly reduced the latency to eat the food pellet in the novelty suppressed feeding test.
In plain wordsIn mice, PE 22‑28 given for 4 days shortened the time to start eating in a feeding test used to study depression.
Peptide
PE 22-28
Outcome
DecreaseLatency to eat in the novelty suppressed feeding test
Study
mousen: not reported in source
novelty suppressed feeding test
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
Dose not stated · 4 days (sub-chronic)As given in this study (mouse).
Source sentences
Summary
Moreover, in the novelty suppressed feeding test after a 4-day sub-chronic treatment PE 22-28 reduced significantly the latency to eat the food pellet.
Show in the study text Report a problemFND-2895524204
02LabIn vitro (cells)Activity measurement
In hTREK-1/HEK cells, PE 22‑28 showed better specificity and affinity for the TREK-1 channel than spadin, with an IC50 of 0.12 nM versus 40-60 nM for spadin.
In plain wordsIn lab tests, PE 22‑28 blocked the TREK-1 channel at much lower amounts than spadin.
Peptide
PE 22-28
Outcome
Not applicableTREK-1 inhibition (IC50) in hTREK-1/HEK cells
Study
n: not reported in source
hTREK-1/HEK cells, patch-clamp
Comparator
Spadin
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Measurements
IC50
0.12 nM
PE 22-28, hTREK-1/HEK cells
IC50
40 to 60 nM
spadin, hTREK-1/HEK cells
Source sentences
Summary
In vitro studies on hTREK-1/HEK cells by using patch-clamp technique, showed that PE 22-28 displayed a better specificity and affinity for TREK-1 channel compared to spadin, IC₅₀ of 0.12 nM vs. 40-60 nM for spadin.
Show in the study text Report a problemFND-2895524201

Studies that did not test the peptide alone5

In this study, PE 22-28 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking PE 22-28.

03AnimalNot a test of PE 22-28 aloneAnimal study (in vivo)Efficacy outcome
In mice in the forced swimming test, PE 22‑28 and its derivatives, pooled, showed antidepressant properties, and spadin analogs significantly reduced immobility time.
In plain wordsIn mice, PE 22‑28 and its derivatives together reduced the time spent immobile in a forced swimming test.
Peptide
PE 22-28
Outcome
DecreaseAntidepressant effect in the forced swimming test (immobility time)
Study
mousen: not reported in source
forced swimming test
Outcome group
Anxiety and mood · Mental health and mood
Source sentences
Summary
In vivo, the antidepressant properties of PE 22-28 and its derivatives were demonstrated in behavioral models of depression, such as the forced swimming test.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice treated with spadin-analogs showed a significant reduction of the immobility time.
In this study, PE 22-28 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PE 22-28.
Show in the study text Report a problemFND-2895524203
04AnimalNot a test of PE 22-28 aloneAnimal study (in vivo)Mechanism
In mice, PE 22‑28 and its analogs, pooled, induced neurogenesis after a 4-day treatment, with a prominent effect of G/A-PE 22‑28.
In plain wordsIn mice, PE 22‑28 and its analogs together increased new nerve cell growth after 4 days, most strongly with the G/A form.
Peptide
PE 22-28
Outcome
IncreaseNeurogenesis after 4-day treatment
Study
mousen: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
PE 22-28 and its analogs were able to induce neurogenesis after only a 4-day treatment with a prominent effect of the G/A-PE 22-28.
In this study, PE 22-28 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PE 22-28.
Show in the study text Report a problemFND-2895524205
05AnimalNot a test of PE 22-28 aloneAnimal study (in vivo)Pharmacokinetics
PE 22‑28 and its analogs, pooled, had a largely improved action duration compared with spadin, up to 23 h instead of 7 h.
In plain wordsPE 22‑28 and its analogs together acted longer than spadin, up to 23 hours instead of 7 hours.
Peptide
PE 22-28
Outcome
IncreaseDuration of action
Study
mousen: not reported in source
in vivo antidepressant models
Comparator
Spadin
Outcome group
Pharmacokinetics · Pharmacology
Measurements
action duration
≤ 23 h
PE 22-28 and analogs
action duration
7 h
spadin
Source sentences
Summary
Finally, the action duration of PE 22-28 and its analogs was largely improved in comparison with that of spadin, up to 23 h instead of 7 h.
In this study, PE 22-28 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PE 22-28.
Show in the study text Report a problemFND-2895524207
06LabNot a test of PE 22-28 aloneIn vitro (cells)Activity measurement
In hTREK-1/HEK cells, different modifications of the N or C-terminal ends of PE 22‑28 maintained or abolished TREK-1 channel activity without affecting affinity.
In plain wordsIn lab tests, changing the ends of PE 22‑28 kept or removed its effect on the TREK-1 channel, with no change in affinity.
Peptide
PE 22-28
Outcome
MixedTREK-1 activity after N or C-terminal modifications
Study
n: not reported in source
hTREK-1/HEK cells, patch-clamp
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
In the same conditions, we also pointed out that different modifications of its N or C-terminal ends maintained or abolished TREK-1 channel activity without affecting PE 22-28 affinity.
In this study, PE 22-28 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PE 22-28.
Show in the study text Report a problemFND-2895524202
07LabNot a test of PE 22-28 aloneIn vitro (cells)Mechanism
In mouse cortical neurons, PE 22‑28 and its derivatives, pooled, enhanced synaptogenesis measured by increased PSD-95 expression.
In plain wordsIn mouse nerve cells, PE 22‑28 and its derivatives together increased a marker of new nerve connections.
Peptide
PE 22-28
Outcome
IncreaseSynaptogenesis (PSD-95 expression)
Study
mousen: not reported in source
cortical neurons
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
On mouse cortical neurons, PE 22-28 and its derivatives enhanced synaptogenesis measured by the increase of PSD-95 expression level.
In this study, PE 22-28 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PE 22-28.
Show in the study text Report a problemFND-2895524206

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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Keywords

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