Involvement of G_q/11 in signal transduction in the mammalian vomeronasal organ

Social behaviors of most mammals are profoundly affected by pheromones. Pheromones are detected by G-protein coupled receptors in the vomeronasal organ (VNO). To investigate the role of Gα_q/11 in vomeronasal signal transduction pathways, microvillar membranes from murine VNO were prepared. Incubation of such membranes from prepubertal females with adult male urine results in an increase in production of inositol-(1,4,5)-trisphosphate (IP₃). This stimulation is mimicked by GTPγS, blocked by GDPβS and is tissue specific. Furthermore, use of bacterial toxins such as pertussis that lead to ADP-ribosylation of the G-protein alpha subunits of G_o and G_i2 do not block the increase in IP₃ levels but U-73122, a PLC inhibitor, blocks the production of IP₃. Studies with monospecific antibodies revealed the presence of three G-proteins, Gα_o, Gα_i2and Gα_q/11-related protein, in vomeronasal neurons,concentrated on their microvilli. Our observations indicate that pheromones in male urine act on vomeronasal neurons in the female VNO via a receptor-mediated, Gα_q/11-protein-dependent increase in IP₃ levels.