Infection of human and swine hosts by the intestinal parasite Ascaris represents a significant public health and economic problem world-wide. The adult organism is largely anaerobic, subsisting on available carbohydrate substrates during the host-feeding cycle and mobilizing endogenous glycogen during non-feeding periods. This investigator has established that 5-hydroxytryptamine (5-HT) is the hormone in Ascaris which initiates glycogenolysis in response to a failing energy charge in Ascaris. This application proposes to investigate the origin of the 5-HT. There are two viable possibilities for where the 5-HT is synthesized. One: the 5-HT is synthesized in the tissue of Ascaris. If this is true, the enzymes for the synthesis of 5-HT from tryptophan as well as the intermediate metabolites must be present. These questions will be investigated using both histochemical localization of 5-HT and biochemical analysis of the enzymes and metabolites. Second: the 5-HT is synthesized by the host and absorbed by the Ascaris. If this is true, 5-HT receptors must be present in Ascaris tissue for the uptake of the 5-HT. The application will investigate whether or not these receptors exist in Ascaris. These results will be correlated with and substantiated by the results obtained using an in situ perfusion system of Ascaris tissue developed by this investigator. The perfusion system permits a systematic variation in external metabolic signals in an attempt to correlate external stimuli with an internal biochemical event. This correlation will be utilized to provide an in-depth understanding of the regulation of 5-HT synthesis, utilization and metabolism and the significance of these events to the organism's survival. Collectively, the data will provide a biochemical basis for the development of chemotherapeutic agents which diminish the parasite's survival by selectively inhibiting the key regulation signal (5-HT) required for the initiation of glycogenolysis and, hence, energy production in this parasite.
