We propose to continue our investigation of the behavior and relationships of specific central nervous system (CNS) amino acid neurotransmitters implicated in the central control of ventilation during experimental acid-base imbalance in an anesthetized animal model. Our general hypothesis is that endogenous CNS substances, among which number certain amino acids, contribute directly to central control of respiration via chemical transmission of neural information and are directly related to CNS acid-base homeostasis. We plan to measure the respiratory effects of specific amino acids introduced by ventriculo-sisternal perfusion in the intact animal and to determine CNS endogenous distributions of these amio acids, specifically, the sites and pathways of metabolism during respiratory acid-base imbalance. Our objectives are: a) to quantitate the effects on respiration of specific amio acid neurotransmitters, b) to identify their specific mechanism and sites of action, and c) to delineate their relationships to CNS acid-base homeostasis. Our long-term objective is to contribute to a fundamental understanding of important CNS metabolic functions in the control of respiration and their relationship to hydrogen ion homeostasis, ultimately leading to the development of methods that have clinical diagnostic and therapeutic utility. The significance of this proposed research is derived from three experimentally well-established phenomena: a) the metabolism of amino acids, ammonia, and CO2 in the CNS are interrelated, b) specific amio acids (GABA and glutamic acid) affect neuronal function, including respiratory drive, and c) hydrogen ion concentration affects respiration, which is, at the same time, modified by other metabolic events in the CNS. This research will clarify the relationship between these three phenomena.
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