Vasoactive intestinal peptide (VIO) and growth factors associated with the action of this neuropeptide were studied as mediators of neuron-glia interactions. Primary cell cultures derived from the mammalian central nervous system were utilized as both test systems and as a source for a newly discovered growth factor, Activity Dependent Neurotrophic Factor (ADNF). Several lines of evidence indicate that ADNF is a potent and novel substance distinct from other known growth factors. Peptide fragments from V-8 digests of ADNF have been sequences and found to exhibit no sequence homology to known growth factors. Neuronal cell death produced by neutralizing antiserum to ADNF was prevented by co- treatment with ADNF; whereas other growth factors (NGF, FGF, PDGF IGF I and II) did not attenuate the antiserum-associated toxicity. Studies of our VIP antagonist were extended to growth inhibition of lung cancer cell lines. Treatment of the lung cancer cells with a VIP antagonist inhibited growth both in vitro and in xenograft formation in nude mice. Vasoactive intestinal peptide levels in serum fluctuate ten-fold during the course of pregnancy in rats. Highest levels in the dams were observed on day 15 and 18 of gestation. In situ hybridization was used to compare the expression of all known alpha adrenergic receptors in rat. The alpha-1 receptors exhibited a more selective expression in the brain than that observed for alpha-2 receptors. Both GTP and GTP- sensitive VIP receptors were observed by gestational day 14 in rats. Their appearance is distinct both temporally and spatially. The transient appearance of dense GTP-insensitive VIP binding was correlated with gliogenesis and glial fasciculation. CNS cultures were also used to study the mechanism of neuronal degeneration in L-tryptophan eosinophilia myalgia syndrome. A metabolic product of a contaminant found in L-tryptophan dietary supplements produced neurotoxicity in mature spinal cord cultures. The toxic effect was prevented by co- treatment with neutralizing antiserum to interleukin-1 alpha.
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