Pure and Applied Chemistry

Abstract: Pheromonal signals received by the vomeronasal organ (VNO) have been shown to elicit various behavioral and physiological responses that are typically stereotyped and preprogrammed. Recently, we found a novel male-specific peptide, named exocrine gland-secreting peptide 1 (ESP1), that is secreted in tear fluid and stimulates the VNO in mice. Excreted ESP1 appears to be transferred to the female VNO, where it induces c-Fos expression and elicits an electrical response in a small subset of vomeronasal sensory neurons (VSNs). We report here the identification of molecular components expressed in ESP1-stimulated VSNs by double-staining with c-Fos. We found that the c-Fos-induced cells were localized amongst the Gαo-expressing VSNs. Furthermore, the ESP1 signal was received by VSNs expressing a single type of vomeronasal receptor type 2 (V2Rp5). Finally, double in situ hybridization of the V2Rp5 and various members of the M1 and M10 families of major histocompatibility complex (MHC) class Ib molecules revealed that V2Rp5-expressing VSNs can express multiple MHC molecules. These results suggest that a V2R rather than MHC molecule is mainly responsible for the recognition of ESP1. The identification of the putative sex-pheromone ESP1 and its cognate receptor therefore will help clarify the molecular mechanisms underlying pheromone recognition in the mouse vomeronasal system.