Cargando…
NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases
Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778182/ https://www.ncbi.nlm.nih.gov/pubmed/35055082 http://dx.doi.org/10.3390/ijms23020892 |
_version_ | 1784637256751906816 |
---|---|
author | Belinskaia, Mariia Zurawski, Tomas Kaza, Seshu Kumar Antoniazzi, Caren Dolly, J. Oliver Lawrence, Gary W. |
author_facet | Belinskaia, Mariia Zurawski, Tomas Kaza, Seshu Kumar Antoniazzi, Caren Dolly, J. Oliver Lawrence, Gary W. |
author_sort | Belinskaia, Mariia |
collection | PubMed |
description | Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca(2+)-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca(2+)-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca(2+)-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca(2+)-dependent exocytosis at different intensities of stimulation. |
format | Online Article Text |
id | pubmed-8778182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87781822022-01-22 NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases Belinskaia, Mariia Zurawski, Tomas Kaza, Seshu Kumar Antoniazzi, Caren Dolly, J. Oliver Lawrence, Gary W. Int J Mol Sci Article Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca(2+)-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca(2+)-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca(2+)-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca(2+)-dependent exocytosis at different intensities of stimulation. MDPI 2022-01-14 /pmc/articles/PMC8778182/ /pubmed/35055082 http://dx.doi.org/10.3390/ijms23020892 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Belinskaia, Mariia Zurawski, Tomas Kaza, Seshu Kumar Antoniazzi, Caren Dolly, J. Oliver Lawrence, Gary W. NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases |
title | NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases |
title_full | NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases |
title_fullStr | NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases |
title_full_unstemmed | NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases |
title_short | NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases |
title_sort | ngf enhances cgrp release evoked by capsaicin from rat trigeminal neurons: differential inhibition by snap-25-cleaving proteases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778182/ https://www.ncbi.nlm.nih.gov/pubmed/35055082 http://dx.doi.org/10.3390/ijms23020892 |
work_keys_str_mv | AT belinskaiamariia ngfenhancescgrpreleaseevokedbycapsaicinfromrattrigeminalneuronsdifferentialinhibitionbysnap25cleavingproteases AT zurawskitomas ngfenhancescgrpreleaseevokedbycapsaicinfromrattrigeminalneuronsdifferentialinhibitionbysnap25cleavingproteases AT kazaseshukumar ngfenhancescgrpreleaseevokedbycapsaicinfromrattrigeminalneuronsdifferentialinhibitionbysnap25cleavingproteases AT antoniazzicaren ngfenhancescgrpreleaseevokedbycapsaicinfromrattrigeminalneuronsdifferentialinhibitionbysnap25cleavingproteases AT dollyjoliver ngfenhancescgrpreleaseevokedbycapsaicinfromrattrigeminalneuronsdifferentialinhibitionbysnap25cleavingproteases AT lawrencegaryw ngfenhancescgrpreleaseevokedbycapsaicinfromrattrigeminalneuronsdifferentialinhibitionbysnap25cleavingproteases |