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PE-22-28: TREK-1 Channel Research and Antidepressant Mechanisms
May
- PE-22-28 is a synthetic spadin analogue derived from the sortilin propeptide, with molecular weight approximately 800 Da.
- Acts as a TREK-1 (TWIK-related potassium channel-1) blocker — depolarising TREK-1-expressing neurons including serotonergic neurons of the dorsal raphe nucleus.
- Research framework for rapid-onset antidepressant mechanisms distinct from SSRI monoamine reuptake inhibition.
What is PE-22-28?
PE-22-28 is a synthetic analogue of spadin — a naturally occurring fragment cleaved from the sortilin propeptide. With a molecular weight of approximately 800 Da, the compound functions as a TREK-1 (TWIK-related potassium channel-1) blocker. TREK-1 is a two-pore-domain background potassium channel implicated in stress-related neurobiology and is a research target of significant interest for rapid-onset antidepressant mechanism investigation distinct from monoamine reuptake inhibition. Researchers can access PE-22-28 research peptide at Advanced Peptide Science within the Cognitive & Neurological category.
Research Background: Spadin and Sortilin
Spadin is a 17-residue peptide naturally cleaved from the propeptide region of sortilin — a transmembrane receptor protein involved in protein trafficking and neurotrophic-factor signalling. Spadin selectively blocks TREK-1 channels, supporting a regulatory role in TREK-1 signalling. PE-22-28 was engineered as a stabilised synthetic spadin analogue retaining the TREK-1-blocking activity for research applications. The compound provides a research tool for investigating TREK-1 channel pharmacology with stability properties suitable for in vitro and in vivo research designs.
Mechanism of Action
Mechanism research investigates PE-22-28 selective blockade of the TREK-1 channel. TREK-1 is a member of the two-pore-domain potassium channel family (K2P), providing “leak” potassium currents that maintain resting membrane potential in many neurons. Blocking TREK-1 reduces the leak current, leading to neuronal depolarisation and increased firing in TREK-1-expressing neurons. The mechanism is fundamentally distinct from synaptic-transmission modulators (such as SSRIs acting on monoamine reuptake transporters) — TREK-1 blockade modifies intrinsic neuronal excitability rather than synaptic signalling.
Key Research Findings
Dorsal Raphe Nucleus Serotonergic Neuron Depolarisation
TREK-1 is expressed in serotonergic neurons of the dorsal raphe nucleus — the principal source of serotonergic projections to forebrain regions. Blocking TREK-1 in these neurons depolarises them, increasing serotonergic firing rates and downstream serotonin release in target regions. The mechanism elevates serotonergic signalling without requiring serotonin transporter (SERT) inhibition.
Rapid-Onset Mechanism
SSRI antidepressants act via SERT inhibition but require weeks of administration to produce therapeutic effects — reflecting downstream adaptations to elevated synaptic serotonin rather than the SERT inhibition itself. TREK-1 blockade directly increases serotonergic neuron firing, potentially providing a faster-onset research mechanism. Comparative research investigates the time-course differences between TREK-1 blockade and SERT inhibition for antidepressant-pathway research.
Two-Pore-Domain Potassium Channel Pharmacology
PE-22-28 is a selective TREK-1 blocker among the K2P channel family — providing a research-tool for dissecting TREK-1-specific vs broader K2P-mediated effects on neuronal excitability. Comparative research uses non-selective K2P blockers to identify TREK-1-specific contributions.
Research Applications
PE-22-28 research applications include TREK-1 channel pharmacology, rapid-onset antidepressant mechanism investigation, sortilin propeptide / spadin signalling research, stress-related neurobiology preclinical model studies, and comparative two-pore-domain potassium channel pharmacology. The Cognitive & Neurological category at Advanced Peptide Science includes complementary research compounds Semax, Selank, Dihexa, and Cerebrolysin for multi-mechanism CNS research frameworks.
Research Specifications
| Molecular Weight | ~800 Da |
| Origin | Synthetic spadin analogue (sortilin propeptide-derived) |
| Primary Target | TREK-1 (TWIK-related potassium channel-1) |
| Mechanism Class | K2P channel blocker |
| Format | Lyophilized powder in sterile vial |
| Purity | ≥ 99% (HPLC verified) |
| Storage | -20 °C, protect from light |
Frequently Asked Questions
What is TREK-1?
TREK-1 (TWIK-related potassium channel-1) is a member of the two-pore-domain potassium channel family (K2P). It provides a “leak” potassium current that maintains resting membrane potential. Blocking TREK-1 depolarises expressing neurons and increases their firing rates.
How does PE-22-28 mechanism differ from SSRIs?
SSRIs inhibit the serotonin reuptake transporter (SERT) at synapses. PE-22-28 blocks TREK-1 channels in serotonergic neuron cell bodies, increasing intrinsic firing rates. The mechanisms are fundamentally distinct — SERT inhibition modifies synaptic transmission; TREK-1 blockade modifies neuronal excitability.
Where can researchers source PE-22-28?
PE-22-28 research peptide is available at Advanced Peptide Science at 99%+ HPLC-verified purity in 1mg and 5mg vials plus kit configurations.
Is PE-22-28 approved for human use?
Advanced Peptide Science supplies PE-22-28 exclusively for in vitro and in vivo scientific research. Not for human consumption. Research use only.
For Research Use Only. Not for human consumption. Not intended to diagnose, treat, cure, or prevent any disease.
