Abstract
BackgroundExtracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation.ResultsHere we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells.ConclusionOur results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.
Highlights
Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling
Odorants induce CREB phosphorylation in the olfactory epithelium The cAMP response element binding protein (CREB) is a well-characterized transcription factor which is activated upon phosphorylation at residue Ser-133, an event induced by various extracellular signals [32]
Exposing mice to a concentration of this odorant mix that was previously shown to evoke physiological responses in the olfactory epithelium (OE) [30], we observed an increase in the phosphorylation of p42/44 MAPK in the cytosol of olfactory sensory neurons (OSN), which was not observed in neurons of untreated mice (Figure 1A)
Summary
Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. Odorant-specific signal transduction is mediated via the olfactory G protein Gaolf [10], adenylyl cyclase type III activation [11], the concomitant cAMP-mediated activation of a cyclic nucleotide-gated (CNG) channel [12,13,14,15] and the opening of a Ca2+ gated Cl- channel [16,17]. The OE is made up of 3 main cell types: OSNs, basal cells which maintain the regenerative capacity of the OE [18,19] and glial-like sustentacular supporting cells. It is likely that sustentacular cells, as is the case for other glial subtypes of the nervous system, function in the maintenance and support of OSNs and play a role in intercellular signalling mechanisms
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