Protein Kinase Cα Is Required for Vanilloid Receptor 1 Activation
By Z. Oláh, L. Kárai, M. Iadarola. Journal of Biological Chemistry, 2002
108 citations recorded by the source corpus.
Activation of vanilloid receptor (VR1) by protein kinase C (PKC) was investigated in cells ectopically expressing VR1 and primary cultures of dorsal root ganglion neurons. Submicromolar phorbol 12,13-dibutyrate (PDBu), which stimulates PKC, acutely activated Ca2+ uptake in VR1-expressing cells at pH 5.5, but not at mildly acidic or neutral pH. PDBu was antagonized by bisindolylmaleimide, a PKC inhibitor, and ruthenium red, a VR1 ionophore blocker, but not capsazepine, a vanilloid antagonist indicating that catalytic activity of PKC is required for PDBu activation of VR1 ion conductance, and is independent of the vanilloid site. Chronic PDBu dramatically down-regulated PKCα in dorsal root ganglion neurons or the VR1 cell lines, whereas only partially influencing PKCβ, -δ, -ε, and −ζ. Loss of PKCα correlated with loss of response to acute re-challenge with PDBu. Anandamide, a VR1 agonist in acidic conditions, acts additively with PDBu and remains effective after chronic PKC down-regulation. Thus, two independent VR1 activation pathways can be discriminated: (i) direct ligand binding (anandamide, vanilloids) or (ii) extracellular ligands coupled to PKC by intracellular signaling. Experiments in cell lines co-expressing VR1 with different sets of PKC isozymes showed that acute PDBu-induced activation requires PKCα, but not PKCε. These studies suggest that PKCα in sensory neurons may elicit or enhance pain during inflammation or ischemia.
Subfields: Molecular Biology, Physiology, Sensory Systems
View Paper: https://www.semanticscholar.org/paper/81aa28d7303971f636a762e5a25f0d4f53c8c000
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Citations in the corpus
- Anandamide and vanilloid TRPV1 receptors (2003, background): “While anandamide activates TRPV1 receptors in cultures in which PKCa is downregulated, it is four-fold less potent and this may implicate PKCa in modulating the potency of anandamide (Olah et al., 2002).”