Cortistatin

Also known as: CST-14, CST-17, CST-29

NeuroprotectivePain & Inflammation

Overview

Cortistatin is a neuropeptide related to somatostatin that is expressed predominantly in cortical interneurons. Unlike somatostatin, cortistatin binds with high affinity to all five somatostatin receptors (SSTR1-5) as well as to MrgX2/MRGPRX2 and the ghrelin receptor (GHS-R1a). In addition to neuroendocrine regulatory functions, cortistatin has potent and novel anti-inflammatory properties mediated through MRGPRX2, making it a research target for inflammatory and autoimmune diseases. Cortistatin-14 is the predominant C-terminal form active in the brain.

Mechanism of Action

Cortistatin activates SSTR1-5 (shared with somatostatin), GHS-R1a (ghrelin receptor), and MRGPRX2. Through SSTR2/SSTR5, it inhibits adenylyl cyclase and suppresses GH/ACTH secretion similar to somatostatin. Via GHS-R1a, it competes with ghrelin and modulates appetite and GH pulsatility. The MRGPRX2 interaction mediates potent anti-inflammatory effects including macrophage deactivation, reduction of IL-12, TNF-α, and IFN-γ production, and promotion of IL-10 and TGF-β tolerogenic cytokines. These anti-inflammatory properties are uniquely cortistatin-specific and not shared by somatostatin.

Potential Benefits

  • Anti-inflammatory effects via MRGPRX2 independent of somatostatin receptors
  • Neuroprotection in inflammatory brain conditions
  • Modulation of cortical excitability and sleep-wake cycles
  • GH and ACTH regulatory activity
  • Potential in rheumatoid arthritis, inflammatory bowel disease, and sepsis models

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

Research context only. No established human dosing.

Amino Acid Sequence

Pro-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Ser-Ser-Cys-Lys (CST-14, cyclic)

Side Effects & Safety

  • Potential hypotension at high doses
  • GH suppression
  • Appetite effects via GHS-R1a

Synergistic Compounds

The following compounds have been studied alongside Cortistatin for potential complementary or synergistic effects:

SomatostatinVIPPACAP

Learn More

Beginner's GuideNew to peptides? Start hereStacking GuideSynergistic combinationsAdministration RoutesSubQ, IM, oral, nasal & moreReconstitution CalculatorCalculate exact dosingPeptides vs SARMsFull comparisonHow Peptides Are MadeSPPS, purification & QC

References & Further Reading

  • [object Object]
  • [object Object]

More Peptides in This Category

SelankSemaxDSIPHumaninDihexaCerebrolysin