Neurohormonal modulation of synaptic transmission adds tremendous flexibility to the already complex pre- and post-synaptic machinery of synapses, and must play important roles in the hormonal orchestration of behavior. Using a lobster model system, we have been exploring the roles served by amines and peptides in such processes. Lobster exoskeletal muscles are under the influence of a large set of hormonal controls. The substances involved, which reach the muscles via the circulation, are two amines, octopamine and serotonin, and several peptides, proctolin, TNRNFLRFamide (a member of the lobster family of FMRFamide-like peptides, which are related to the vertebrate opioid peptides), and peptide G1 (a new peptide the specifically turns on cyclic GMP metabolism in lobsters). All of these change muscle function by exerting unique, long-lasting actions on exoskeletal muscle preparations. With this application we will continue our efforts to unravel the hormonal regulation of these tissues by addressing the following questions: (1) How do newly isolated lobster neurohormonal substances influence pre- and post-synaptic physiology? (2) Do neurohormones interact with each other in important ways? (3) What second messenger mechanisms underlie the actions of the neurohormones? (4) What biochemical changes are induced by activation of these second messengers? (5) Which conductances in muscle fibers are influenced by the hormonal substances? (6) What are the actions of these substances at the single channel level? (7) What are the biophysical and physiological characteristics of newly-formed exoskeletal muscles? (8) When does hormonal responsiveness first appear? (9) Are there specific changes in any of these parameters during the molt cycle? It is well known that drugs that interfere with the actions or metabolism of neurohormonal substances, like amines or peptides, have profound effects on human behavior. Drugs like cocaine, LSD, amphetamines and heroin fall into this category, and their abuse is a serious problem in our society. Moreover, in some cases, we know or suspect that abnormal amine-neuron function in the cause of a major neurological disorder (Eg. loss of dopamine neurons and Parkinson's Disease, excess dopamine and schizophrenia, norepinephrine and serotonin levels and major depressive illness, opioids and pain disorders). Ultimately these effects depend on how amines and peptides act at a synaptic level. Such studies serve as the core of this grant application.
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