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The receptor cells are G-protein-coupled receptors which detect the pheromones, which are frequently referred to as pheromone receptors. The receptor neurons possess apical microvilli whose axons merge together to form VN nerves which move from the paired olfactory bulbs to the main olfactory bulb, entering the posterior dorsal aspect through the AOB. There have been two different G-protein-coupled receptors identified in the VNO, each found in distinct regions. These are V1 and V2. V1 and V2 are seven transmembrane receptors which are not closely related to the main olfactory receptors.

  • V1 receptors, V1Rs, are linked to the G protein, Gαi2. V1Rs are located on the apical compartment of the VNO. They have a relatively short NH2 terminal and have a great sequence diversity in their transmembrane domains.
  • 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 pheomonal molecules. V2Rs make up a large family of around 140 different genes that are known for this long extracellular amino terminus. V2Rs are located on the basal compartment of the VNO. V2R genes can be grouped in to four separate families, termed A, B, C (also known as V2R2), and D. Family C V2Rs are quite distinct from the other families and they are expressed in all 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.

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) 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 volatile oderents.
  • Go proteins on the other hand is activated by nonvolatile proteins, suggesting that V2Rs are activated by non volatile proteins.

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