Opioid compounds, in addition to their analgesic and behavioral effects, have an important function in the regulation of growth particularly in developing neural systems. Although it is not known which of the endogenous neuropeptides are involved in this process, evidence indicates a prominent role for endorphin compounds.
The aim of the proposed studies is to identify the neuropeptides involved in cell development and to elucidate the mechanism(s) by which they express this control. We propose to characterize the effects of beta-endorphin and N alpha-acetyl-beta-endorphin on basal ornithine decarboxylase (ODC) activity on brain, liver, heart and kidney during ontogeny. ODC catalyzes the initial step in the synthesis of the polyamines, which are major regulators of macromolecular synthesis. The metabolic consequences of the changes in ODC will be assessed through evaluation of nucleic acid and protein synthesis. cAMP and tyrosine amino-transferase levels will be measured to determine whether the changes in ODC reflect a general alteration in cell metabolism or a specific intracellular action distal to cAMP generation. We will determine whether opioid and/or non-opioid mechanisms mediate these actions of neuropeptides. To establish whether neuropeptides influence development through actions on trophic hormones the effects of endorphins on plasma levels of insulin and growth hormone as well as on tissue sensitivity to these substances will be determined. To investigate whether the effects of neuropeptides on peripheral tissues are mediated by endocrine/neuronal signals originating in the CNS, similar studies will be conducted in hypophysectomized animals (as young as 4 days of age). These studies will clarify the role of the pituitary gland on developmental effects of neuropeptides. Finally, we will characterize the structural requirements of neuropeptides to elicit their actions on growth. Identification of the """"""""minimal"""""""" fragment of the neuropeptide molecule required to influence development as well as small peptide forms with potential growth-regulatory properties are expected from this part of the investigation. In summary, these studies will identify endogenous neuropeptides capable of regulating specific biochemical/endocrine/physiological processes intimately related to cell growth and development. These findings should provide important information for understanding events involved in normal and abnormal growth.
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