Functional endothelin receptors are selectively expressed in isolectin B4-negative sensory neurons and are upregulated in isolectin B4-positive neurons by neurturin and glia-derived neurotropic factor

• Published in: Brain research 2011-03, Vol.1381, p.31-37
• Main Authors: Vellani, Vittorio, Prandini, Massimiliano, Giacomoni, Chiara, Pavesi, Giorgia, Ravegnani, Laura, Magherini, Pier Cosimo
• Format: Article
• Language: English
• Subjects: Animals; antagonists; Biological and medical sciences; brain; calcium; Calcium - metabolism; Cells, Cultured; cytoplasm; Endothelin-1 - pharmacology; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; GDNF; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Glycoproteins - metabolism; Hyperalgesia; immunocytochemistry; Immunohistochemistry; Isolectin B4; Lectins - metabolism; Medical sciences; nerve growth factor; Nerve Growth Factor - pharmacology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurturin; Neurturin - pharmacology; NGF; Peripheral glial cell; PKCε; plasma membrane; Protein Kinase C-epsilon - metabolism; Protein Transport - drug effects; Protein Transport - physiology; Rats; Rats, Sprague-Dawley; receptors; Receptors, Endothelin - metabolism; Schwann cells; sensory neurons; Sensory Receptor Cells - cytology; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.01.019

Abstract Activation of endothelin receptors expressed in DRG neurons is functionally coupled to translocation of PKCε from cytoplasm to the plasma membrane. Using immunocytochemistry we show that in DRG cultured neurons PKCε translocation induced by endothelin-1 was prominently seen in a peptidergic subpopulation of cultured DRG neurons largely negative for isolectin B4 staining, indicating that in basal conditions functional expression of endothelin receptors does not occur in non-peptidergic, RET-expressing nociceptors. Translocation was blocked by the specific ETA-R antagonist BQ-123 while it was unaffected by the ETB-R antagonist BQ-788. No calcium response in response to endothelin-1 was observed in sensory neurons, while large and long-lasting responses were observed in the majority of non-neuronal cells present in DRG cultures, which are ensheathing Schwann cells and satellite cells, identified with the glial marker S-100. Calcium responses in non-neuronal cells were abolished by BQ-788. The fraction of peptidergic PKCε-translocated neurons was significantly increased by nerve growth factor, while in the presence of neurturin or glia-derived neurotropic factor (GDNF), an IB4-positive subpopulation of small- and medium-sized neurons showed PKCε translocation induced by endothelin-1 which could be blocked by BQ-123 but not by BQ-788. Our in vitro results show that the level of expression of functional endothelin receptors coupled to PKCε is different in peptidergic and non-peptidergic nociceptors and is modulated with different mechanisms in distinct neuronal subpopulations.