Endothelin uncouples gap junctions in sustentacular cells and olfactory ensheathing cells of the olfactory mucosa

Abstract

Several factors modulate the first step of odour detection in the rat olfactory mucosa (OM). Among others, vasoactive peptides such as endothelin might play multifaceted roles in the different OM cells. Like their counterparts in the central nervous system, the olfactory sensory neurons are encompassed by different glial-like non-neuronal OM cells; sustentacular cells (SCs) surround their cell bodies, whereas olfactory ensheathing cells (OECs) wrap their axons. Whereas SCs maintain both the structural and ionic integrity of the OM, OECs assure protection, local blood flow control and guiding of olfactory sensory neuron axons toward the olfactory bulb. We previously showed that these non-neuronal OM cells are particularly responsive to endothelin in vitro. Here, we confirmed that the endothelin system is strongly expressed in the OM using in situ hybridization. We then further explored the effects of endothelin on SCs and OECs using electrophysiological recordings and calcium imaging approaches on both in vitro and ex vivo OM preparations. Endothelin induced both robust calcium signals and gap junction uncoupling in both types of cells. This latter effect was mimicked by carbenoxolone, a known gap junction uncoupling agent. However, although endothelin is known for its antiapoptotic effect in the OM, the uncoupling of gap junctions by carbenoxolone was not sufficient to limit the cellular death induced by serum deprivation in OM primary culture. The functional consequence of the endothelin 1-induced reduction of the gap junctional communication between OM non-neuronal cells thus remains to be elucidated.

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

“…Their particular role and function still needs to be elucidated. While OEC wrap around OSN axons, SUS are enclosed around OSN dendrites, to ensure structural stability and to maintain ionic integrity [ 41 , 42 ]. Enwrapping occurs with OSN maturation: while most of the immature OSN dendrites are unwrapped, the majority of mature OSN dendrites are enwrapped with SUS [ 41 ].…”

“…Endothelin signaling provides a way of SUS and OEC damage control [ 42 ]. Endothelin also acts as survival factor, it uncouples gap junctions between SUS enwrapping adjacent OSN to limit cell death [ 42 ].…”

Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro

“…We first investigated the olfactory epithelium (OE), since little is known about the initial cellular responses of the olfactory gateway to urban traffic-derived ultrafine (or, equivalently) nPM. Based on the precedent of ex vivo OE incubation from OE biopsies [ 26 , 27 ], we developed an ex vivo model for incubation of the intact OE within neonatal mouse nasal cavities with nPM suspensions. In addition, using glia and neurons derived from neonatal cerebral cortex, we analyzed mechanisms by which nPM-induced TNFα inhibits neurite outgrowth.…”

Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine

“…Olfactory-sensitive neurons and their axons are enveloped by glia-like cells called sustentacular cells, which help to sustain the olfactory mucosa (OM) structure and ionic integrity [ 17 ]. A group demonstrated that sustentacular cells were sensitive to ET-1 and thereby able to uncouple gap junctions [ 288 , 289 ]. Moreover, endothelin has been described to inhibit gap junctional communication effectively in astrocytes [ 290 ].…”