Vomeronasal - Sensory Epithelium and Receptors

Sensory Epithelium and Receptors

The VNO is a tubular crescent shape and split into two pairs, separated by the nasal septum. The medial, concave area of the lumen is lined with a pseudo stratified epithelium that has three main cell types: receptor cells, supporting cells, and basal cells. The supporting cells are located superficially on the membrane while the basal cells are found on the basement membrane near the non sensory epithelium. The receptor neurons possess apical microvilli, to which are localized the sensory receptors, G-protein-coupled receptors which are often referred to as pheromone receptors since vomeronasal receptors have been tied to detecting pheromones.

There have been three different G-protein-coupled receptors identified in the VNO, each found in distinct regions: the V1Rs, V2Rs, and FPRs. V1Rs, V2Rs and FPRs are seven transmembrane receptors which are not closely related to odorant receptors expressed in the main olfactory neuroepithelium.

• V1 receptors, V1Rs, are linked to the G protein, Gαi2. The benefit of the GPCR is that they signal in more than one direction. V1Rs are located on the apical compartment of the VNO and a relatively short NH2 terminal and have a great sequence diversity in their transmembrane domains. V1R is specifically expressed in the rodent vomeronasal organ (VNO) and is thought to be responsible for pheromone reception, eliciting a signal tranduction.

• V2 receptors, V2Rs, are linked to the G-protein, Gαo. These have long extracellular NH2 terminals which are thought to be the binding domain for pheromonal molecules, and are located on the basal compartment of the VNO. V2R genes can be grouped in to four separate families, labelled A - D. Family C V2Rs are quite distinct from the other families and they are expressed in most basal neurons of the VNO.

The vomeronasal organ’s sensory neurons act on a different signaling pathway than that of the main olfactory system’s sensory neurons. Activation of the receptors stimulates phospholipase C, which in turn opens the ion channel TRPC2. Upon stimulation activated by pheromones, IP3 production has been shown to increase in VNO membranes in many animals, while adenylyl cyclase and cyclic adenosine monophosphate (cAMP), the major signaling transduction molecules of the main olfactory system, remain unaltered. This trend has been shown in many animals, such as the hamster, the pig, the rat, and the garter snake upon introduction of vaginal or seminal secretions into the environment.

V1Rs and V2Rs are suggested to be activated by distinct ligands or pheromones. The evidence that Gi and Go proteins are activated upon stimulation via different pheromones supports this.

• Gi proteins are activated upon stimulation with lipophilic odorants.
• Go proteins on the other hand is activated by nonvolatile proteins, such as the major urinary proteins of mice and exocrine gland-secreting peptide 1 (ESP1).

Many vomeronasal neurons are activated by chemicals in urine. Some of the active compounds are sulfated steroids. Detecting the types and amounts of different sulfated steroids conveys information about the urine donor's physiological state, and may therefore serve as an honest signal.

Recent studies proved a new family of formyl peptide receptor like proteins in VNO membranes of mice, which points to a close phylogenetic relation of signaling mechanisms used in olfaction and chemotaxis.