Immunocytochemical localization of dopamine-releasing protein in the rat adrenal

The mechanism by which adrenal medulla transplants to the brain of Parkinson's patients ameliorate the symptoms of this neurodegenerative disease is unknown. It has been postulated but not proven that these transplants secrete a neurotrophic factor(s) responsible for the activation of the dopamine (DA) neurons. DA-releasing protein (DARP) was identified by immunocytochemistry in cells of the adrenal gland but not in tissues such as the liver or spleen. In the adrenal gland the immunopositive DARP cells were distributed both in the cortex as well as in the medulla. In the former, the distribution was rather uniform covering a broad area of the zona glomerulosa and fasciculata without positive cells in the zona reticularis. In the adrenal medulla the DARP signal was found in segregated cells forming clusters similar to the homotypic distribution of norepinephrine and epinephrine cells. The immunopositive cells for DARP were oval or spindle in shape and the staining was localized in the cytoplasm surrounding the nucleus. In addition, in this paper we present evidence confirming that the adrenal gland is the source of a protein that after immunopurification in nanogram amounts releases DA from corpus striatum fragments superfused in vitro. These data clearly demonstrate the existence of DARP in the adrenal gland and support the hypothesis that the effectiveness of the adrenal medulla transplants to the brain of Parkinson's patients is in part due to the secretion of neurotrophic factors. We submit that DARP is one of such factors.