VASOACTIVE-INTESTINAL-PEPTIDE - AN IMPORTANT TROPHIC FACTOR AND DEVELOPMENTAL REGULATOR

It has been proposed that vasoactive intestinal peptide (VIP) or a very closely related peptide has important actions very early in embryonic development. Recent data supporting this hypothesis are that subnanomolar concentrations of VIP significantly increased the growth rate of cultured embryonic day-9.5 (E9.5) mouse embryos, and that embryos at this and later stages exhibit a high degree of VIP binding in the brain stem and spinal cord. It is not known whether VIP is derived from the fetus, placenta, or mother at these early stages, or whether VIP acts in this culture system in place of a related peptide. The earliest reported expression of VIP in rat embryos is at E13.5, when the peptide and mRNA are expressed transiently in a high percentage of cells in the rat stellate ganglia. The time course of events mapped in other sympathetic ganglia at this stage suggest that transient expression of VIP in the ganglia might function to regulate neuroblast and/or glial cell proliferation, maturation or survival. Tissue culture studies indicate that VIP can support many of these trophic functions at concentrations that are the same or lower than that necessary to increase cAMP levels by way of classical VIP receptors. For example, VIP at 10(-10) M stimulates the release of neurotrophic factors from glial cells and maximally stimulates the proliferation of astrocytes. Two VIP receptors encoded on different genes have now been cloned. Both are members of the seven transmembrane G-protein-coupled receptor family and, when expressed in mammalian cells, mediate an increase in cAMP. Cloned forms of each receptor have also been shown to mediate increased intracellular calcium or activate a calcium-activated chloride channel. These or other forms of the receptor may mediate the trophic activities of VIP.