NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases.

Abstract

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 Ca2+-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 Ca2+-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 Ca2+-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 Ca2+-dependent exocytosis at different intensities of stimulation.

• Authors: Mariia Belinskaia, Tomas Zurawski, Seshu Kumar Kaza, Caren Antoniazzi, J Oliver Dolly, Gary W Lawrence
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 2 (Jan 14 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35055082 (Publication Type: Journal Article)

Chemical References

• Synaptosomal-Associated Protein 25
• Nerve Growth Factor
• Botulinum Toxins, Type A
• Calcitonin Gene-Related Peptide
• Capsaicin
• Calcium

Topics

• Animals
• Botulinum Toxins, Type A (pharmacology)
• Calcitonin Gene-Related Peptide (biosynthesis)
• Calcium (metabolism)
• Calcium Signaling (drug effects)
• Capsaicin (pharmacology)
• Dose-Response Relationship, Drug
• Exocytosis (drug effects)
• Nerve Growth Factor (metabolism, pharmacology)
• Proteolysis
• Rats
• Sensory Receptor Cells (drug effects, metabolism)
• Synaptosomal-Associated Protein 25 (metabolism)
• Trigeminal Ganglion (drug effects, metabolism)