Health Sciences Center
Hospital and Clinic
Primate Center
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(Neuroendocrinology)

Professor of Medicine
Ph.D: Nagoya University
Postdoctoral: Yale University

The major interest of the US-Japan Biomedical Research Labs, Tulane University Hebert Center, is Neuroendocrinology, Neuroendocrine Immunology. The following three projects are in progress in these laboratories.

Since all hypothalamic releasing hormones so far isolated activate adenylate cyclase in the pituitary cell cultures, we postulated that other unknown hypothalamic releasing hormones, if present, would also have such activity. Based on this assumption, we isolated a novel peptide from ovine hypothalamic tissues by assessing such activity in rat pituitary cell cultures. The peptide was named as PACAP38. A shorter form with 27 residues (PACAP27) was also isolated. Synthetic preparations of these peptides were found to possess comparable biological activities as these native peptides. Determination of the primary structure indicated that PACAPs are new members of secretin/ glucagon/VIP family of peptides. PACAP has pleotropic effects on various tissues, including pituitary, neurons, astrocytes, intestines, cardiovascular system, adrenals, immune cells, through its action as a neurotransmitter and neuromodulator. A dense network of PACAP containing neurofibers was found in the dorsal horn of the spinal cord, and PACAP positive neurons in the dorsal root ganglion. Since PACAP immunoreactivity is contained in fine, probably C-fibers, this peptide appears to be involved in sensory signal processing. In addition to these findings, the peptide exhibits growth factor activity in neuronal tissues and neurons. One of the significant actions is complete prevention of neuronal cell death induced by gp12O in vitro. It also stimulates production and release of II-6 from folliculo-stellate cells of the pituitary. Cloning of PACAP precursor was succeeded using sheep, rat and human cDNA library, and the primary structure of PACAP in these species was found identical. Recently we have also succeeded in cloning cDNA of rat and bovine receptor of PACAP. In situ hybridization with immunohistochemistry for PACAP is being conducted using a riboprobe as well as synthetic oligonucleotides.

Interaction between the immune and the neuroendocrine systems: The immune system is not only regulated by cell to cell interaction, it is also regulated by the nervous system. The nervous system is also affected by alteration of the immune response. Our laboratories studied the mechanisms by which the immune signal is transmitted to the central nervous system. Our study has suggested that blood borne interleukin-1 (IL-1) produced by monocytes or phagocytes reaches the brain through organum vasculosum of the lamina terminalis where the immune signal carried by IL-1 beta is transduced to a neuronal signal which then stimulates release of CRH. Using a microdialysis technique, we studied biochemical events at each step of transmission of the immune signal in the brain. Current study includes the study for the effect of non-inflammatory stress and toxicenvironmental wastes on the immune system, particularly regulation of IL-6 production.

Recent Publications:

A PubMed listing of research publications for Akira Arimura, M.D., Ph.D.,

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