Effects of opioid peptides and naloxone on nervous tissue in culture

It was shown that opioid peptides stimulate nervous tissue growth in culture in the rat, which manifests itself in augmented outgrowth of neurites from explants and in an increase in the number of glial and fibroblast-like cells in the growth zone. The effects of opioid peptides ([Leu]- and [Met]-enkephalins, beta- and gamma-endorphins and some synthetic analogues of [Leu]-enkephalin) on the growth of organotypic cultures of rat sympathetic and dorsal root ganglia and spinal cord were investigated. Neurite outgrowth, cell composition, and size of the growth zone as well as the dynamics of its formation were estimated. Changes in the survival of neurons in dorsal root ganglion cultures were determined. The experiments were performed with living cultures as well as with fixed preparations. In experiments with sympathetic ganglia, it was demonstrated that a significant growth-promoting effect is exerted by peptides taken at concentrations of 10(-8) M to 10(-14) M. Naloxone does not eliminate the effects of peptides, but stimulates the growth at 10(-5) M to 10(-7) M. Studies with spinal cord revealed that naloxone (10(-6) M) enhances the response to [Leu]-enkephalin (10(-9) M). The survival of dorsal root ganglion neurons under the influence of a [leu]-enkephalin analog (10(-9) M) exceeds control values by approximately two to four times. Thus, opioid peptides were shown to exert a strong growth-promoting effect on nervous tissue in culture. This effect is dual: in neurons the peptides stimulate the outgrowth of neurites and their survival, while in glial cells they change the rate of their migration and, probably, their proliferation. It is suggested that opioid peptides, besides their already established functions, may play a role in the development and regeneration of nervous tissue.