The hormones vasopressin and oxytocin, which have crucial roles in maintenance of blood volume and osmolality and in various reproductive functions in mammals, are secreted by the magnocellular neuroendocrine cells (MNCs) of the hypothalamo-neurohypophysial system (HNS). The goal of the research proposed here is to investigate some of the receptor-mediated mechanisms that control electrical and secretory activities both at the level of the soma and at the axon terminal. In particular, the research is focussed upon the effects of certain amino acids and dipeptides, including gamma-aminobutyric acid, glutamate, aspartate, N-acetylaspartate (NAA), and N-acetylaspartatylglutamate (NAAG) which may be neurotransmitters in many areas of the CNS including the HNS. To achieve these objectives, whole-cell voltage and current clamp techniques will be used to investigate the nature of the receptors for excitatory and inhibitory amino acids, the nature of receptor-ion channel coupling and the effects of these putative neurotransmitters on the overall electrical activities of MNCs. Recording will be made from dissociated MNCs of the adult rat supraoptic nucleus and from cultured neonatal supraoptic neurons in studies of receptor mechanisms at the level of the cell body in the hypothalamus. Recordings will also be made from isolated axon terminals of the adult neurohypophysis to study mechanisms at the axon terminal. Adult neurons and axon terminals will be obtained from normal rats and from rats where hormone secretion is increased by two physiological stimuli: lactation and dehydration. These electrophysiological studies will be combined with studies on the effects of these putative neurotransmitters may control secretion and also provide insights into how compounds, which may be therapeutically beneficial in stroke and epilepsy, directed at amino acid-mediated receptors and associated ion channels, but with other prime target sites in the CNS, may affect this physiologically important hormone-secreting system.
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