The discovery of the endogenous opiate peptides (endorphins, dynorphin, methionine and leucine-enkephalin being among the most prominent) has led to a detailed search for a physiological function for these substances. It has been suggested that the enkephalins and endorphins may function as neurotransmitters or neuromodulators in the central and peripheral nervous system. Morphine interacts preferentially with mu receptors, whereas the enkephalins interact preferentially with delta receptors. Dynorphin interacts specifically with a third type of opiate receptor, the kappa receptor. Attempts to assign a physiological role to the opiates is complicated by the heterogeneity of receptors and at present the evidence available is not sufficient to assign different receptors to different physiological functions. In this proposal, we will test the effects of morphine, enkephalins, dynorphin, endorphins and other endogenous and synthetic opiate agonists and antagonists in perfused organ systems in which the nerve stimulation mediated release of norepinephrine can be evaluated. Changes in the release of norepinephrine following nerve stimulation will be determined in the isolated perfused cat and rat spleen and adrenal gland, guinea-pig and rat heart and the rat tail artery. These studies will help in elucidating events occurring at nerve endings in organs of different species and aid in determining physiological functions of various opiates. By comparing presynaptic and postsynaptic effects of these opiate agonists and antagonists in perfused organ systems, we hope to assign physiological functions to the various opiate receptors. Blood pressure and heart rate changes in conscious rats will be measured after administration of the opiate agonists and antagonists intraventricularly, and intravenously to attempt to correlate receptor function with physiological parameters. Opiates have extensive effects on behavior and mood and Beta-endorphin is being used clinically for the treatment of a variety of psychiatric illnesses on an experimental basis. A more complete understanding of the physiological roles of the various opiates will aid the treatment of mental illness.
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