# Activity of Peptides Modulating the Action of p2x Receptors: Focus on the p2x7 Receptor

## TL;DR

This review explores how various peptides interact with and modulate the activity of P2X receptors, particularly the P2X7 subtype, which is involved in inflammation and cell death.

## Contribution

The paper provides a comprehensive overview of peptides that modulate P2X receptors, highlighting their diverse mechanisms and effects.

## Key findings

- Peptides like beta-amyloid and LL-37/hCap18 directly modulate P2X7 receptor activity.
- Antimicrobial peptides can influence P2X receptors by interacting with cell membranes and ion channels.
- The review identifies multiple peptides that affect different subtypes of P2X receptors.

## Abstract

P2X receptors are a family of ATP-gated ion channels widely distributed in various tissues, especially in neuronal cells and hematopoietic cells. ATP activates P2X receptors, causing the opening of an ionic channel with preferential permeability to the passage of mono- and divalent cations. High concentrations of ATP stimulate the P2X7 subtype through prolonged activation, which opens pores and causes inflammation, proalgesic effects, and cell death. Peptides, including antimicrobials (antimicrobial peptides), are present in several organisms, such as amphibians, mammals, fish, arachnids, and plants, where they act as the first line of defense. Thus, these peptides have the capacity to eliminate a wide spectrum of microorganisms, such as bacteria, fungi, and some viruses. In general, the mechanism of action of antimicrobial peptides involves interactions with the lipid bilayer of the cell membrane, which can lead to an increase in the internal liquid content of liposomes. However, many peptides can act on ion channels, such as those of the P2X family, especially the P2X7 receptor. We investigated the action of peptides that directly modulate P2X7 receptors, such as beta-amyloid, LL-37/hCap18, Pep19-2.5, rCRAMP, ADESG, and polymyxin B. Additionally, we evaluated peptides that modulate the activity of P2X family receptor subtypes. In this review, we intend to describe the relationships between peptides with distinct characteristics and how they modulate the functionality of P2X receptors.