Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

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.

PROS-1/Prospero Is a Major Regulator of the Glia-Specific Secretome Controlling Sensory-Neuron Shape and Function in C. elegans

“…Glia-like cells in the mammalian taste bud, olfactory epithelium, cochlea and retina, classified as type I cells, sustentacular cells, Deiters’ cells and RPE (retinal pigment epithelial) cells, respectively, show a number of functions typically associated with glia. These include regulating neurotransmitter signaling (Bartel et al, 2006; Dooley et al, 2011; Hegg et al, 2009; Lawton et al, 2000; Matsunobu et al, 2001), buffering extracellular potassium levels (Boettger et al, 2002; Dvoryanchikov et al, 2009; Trotier, 1998) and releasing neurotrophic factors and neuromodulators (Breunig et al, 2010; Hansel et al, 2001; Strauss, 2005). Thus, functional similarities between sense-organ and CNS glia, and similarities between sensory-neuron receptive endings and synapses (Shaham, 2010), suggest that understanding sensory neuron-glia interactions may have broad relevance.…”

Presence of Sex Steroid‐Metabolizing Enzymes in the Olfactory Mucosa of Rats

“…In general, OSCs play roles in the mechanical (Breipohl et al, ; Rafols and Getchell, ; Nomura et al, ) and physiological (Okano and Takagi, ; Getchell, ; Suzuki et al, ) support for ORCs that express odorant receptors (Mombaerts, ) and detect chemical stimuli (Munger et al, ). Furthermore, OSCs are involved in xenobiotic metabolizing function (Chen et al, ; Rama‐Krishna et al, ; Kudo et al, ), protection against stress by expressing heat‐shock proteins (Carr, ), internalization of odorant‐binding proteins (Strotmann and Breer, ), and purinergic pathways (Housley et al, ; Dooley et al, ).…”

P2X4 Receptor Regulates Alcohol-Induced Responses in Microglia

“…Several signaling pathways are coupled to P2 receptors in the CNS including the MAPK/ERK pathway, NGF expression, and calcium mobilization 17, 21-25 . P2X receptors are ubiquitously expressed ligand-gated cation channels that mediate a remarkable variety of physiological and pathophysiological reactions, especially in microglia 16-20, 26 . More recently, purinergic receptors have been implicated in alcohol abuse disorders, affecting signaling in the CNS 27, 28 .…”