Small peptides derived from the autoinhibitory XY linker of phospholipase C-β isoforms inhibit enzyme activity and reduce inflammation
hydrolysis and the consequent calcium release from endoplasmic reticulum. These peptides selectively target PLCβ isoforms, without affecting PLCγ-dependent signaling. In primary nociceptor cultures, active peptides attenuate bradykinin-induced electrogenesis and TRPV1 sensitization reducing nociceptor hyperexcitability. Noteworthy, intraplantar administration of a lead peptide prevented inflammation and hypersensitivity in a mouse model of inflammatory pain, highlighting a therapeutic potential. Collectively, our findings indicate that peptides derived from the autoinhibitory XY linker act as selective PLCβ inhibitors with in vivo anti-inflammatory and antinociceptive activity, providing novel pharmacological tools for this enzyme family.
Authors
- David Cabañero (ORCID: https://orcid.org/0000-0002-1133-0908)
- Jorge de Andrés-López (ORCID: https://orcid.org/0000-0001-7797-4688)
- Nikita Gamper (ORCID: https://orcid.org/0000-0001-5806-0207)
- M. Angeles Bonache
- Shihab Shah (ORCID: https://orcid.org/0000-0002-3639-1133)
- Gregorio Fernandez-Ballester
- Isabel Devesa
- Asia Fernández-Carvajal
- Rosario González-Muñiz
- Antonio Ferrer-Montiel
Institutions
- Universitat de Miguel Hernández d'Elx (ES)
- Hebei Medical University (CN)
- University of Leeds (GB)
- Consejo Superior de Investigaciones Científicas (ES)
- Instituto de Química Médica (ES)
Publication Details
- Journal
- Biomedicine & Pharmacotherapy
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1016/j.biopha.2026.119272
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- Ministerio de Ciencia, Innovación y Universidades
- Biotechnology and Biological Sciences Research Council
- Conselleria de Cultura, Educación y Ciencia, Generalitat Valenciana