ABSTRACT
BACKGROUND: Extracellular 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. RESULTS: Here 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. CONCLUSION: Our 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.
Subject(s)
CREB-Binding Protein/metabolism , Odorants , Olfactory Mucosa/physiology , Olfactory Receptor Neurons/physiology , Purinergic Antagonists/pharmacology , Receptors, Odorant/metabolism , Smell/physiology , Animals , Cells, Cultured , Mice , Olfactory Mucosa/cytology , Olfactory Mucosa/drug effects , Olfactory Receptor Neurons/drug effects , Phosphorylation , Smell/drug effectsABSTRACT
Calcium-activated chloride channels (CaCCs) are involved in many physiological processes, including sensory signal transduction, but only little is known to date about their structure and function. We performed a proteome analysis of the olfactory epithelium (OE) membrane proteome and identified so far uncharacterized membrane proteins as candidate channels. One of the most abundant membrane proteins in olfactory sensory neurons (OSNs) was Tmem16b, a member of a recently identified family of CaCCs. In addition to former studies performed on Tmem16b, we show here that Tmem16b expression is highly specific for the OE, in contrast to the closely related Tmem16a, which shows a broad expression pattern in secretory epithelial cells. Native Tmem16b is localized in the cilia of the OSNs, which is in agreement with previous electrophysiological recordings.
