Effect of derivatives of substance P dipeptide on nerve fiber growth in tissue culture

: Explants and cells from the peripheral (PNS) and central nervous system (CNS) were cultivated in MAXIMOW chambers. The following four derivatives of Substances P (SP) dipeptide were tested for their effects in concentrations between 10(-4) and 10(-8) mol/l: Lys-Pro X 2HBr, Lys(Z)-Pro X HCl, Lys[Z(NO2)]-Pro X HCl and cyclo(Lys-Pro) X HCl. The results suggest that SP and SP derivatives may modulate nerve fibre outgrowth in vitro. In ganglion trigeminale explants Lys(Z)-Pro X HCl stimulated the growth of nerve fibres. The explant covered areas increased significantly. In telencephalon explants and cell cultures the tested derivatives did not essentially promote neurite outgrowth. In retinal cell cultures incubated with cyclo(Lys-Pro) X HCl and Lys[Z(NO2)]-Pro X HCl the neurite outgrowth index was stimulated in a different way. The neurite length was affected and stimulated in the presence of Lys(Z)-Pro X HCl and cyclo(Lys-Pro) X HCl. Both for survival and differentiation PNS neurons depend on specific biofactors. In sensory ganglia explants SP and especially SP derivatives were shown to improve neuronal survival provided that serum or embryonic extract was simultaneously present in the medium. Even if the dipeptides need other biofactors for their full function the may be discussed as neuronotrophic factors because they ensure survival and general growth capability of the responsive neuroblasts.