Kinetics of the co-transport of sodium and phenylalanine in the guinea-pig samll intestine. III - Influence of harmaline on sodium and phenylalanine fluxes.
The effect of harmaline on sodium and phenylalanine influxes in guinea-pig small intestine has been examined kinetically. Harmaline behaves as a fully competitive inhibitor of the saturable component of sodium influx; this property has been revealed from experiments in which the sodium concentration was varied and the harmaline concentration maintained constant, and from a second series in which sodium was constant and harmaline levels were altered. A Ki-value for harmaline of 1.61 mM was deduced from these experiments. The effect of harmaline on phenylalanine influx is more complex, since only that component of entry which occurs in the form of the ternary complex is sensitive to the drug. Within the framework of a non-compulsory model for co-transport which appears to describe phenylalanine influx in this tissue, equations were derived to calculate the different components of influx under given experimental conditions. tJøala, the influx to phenylalanine in the form of the ternary complex, was found to be a Michaelis-Menten function of the sodium concentration. Assuming that the component in the form of the binary complex is unchanged by harmaline, that occurring in the ternary form in the presence of the drug can be evaluated by subtraction. This fraction is also a Michaelis-Menten function of the sodium concentration; the inhibition by harmaline is released on raising the sodium concentration. From these expressions, a Ki for harmaline under these conditions of 1.66 mM was derived. These observations support the proposal that harmaline interferes with the interaction of sodium with its specific sites on the carrier in the intestinal brush-border membrane.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001692:Biological Transport; D002352:Carrier Proteins; D006168:Guinea Pigs; D006246:Harmaline / Q000494:pharmacology*; D007421:Intestine, Small / Q000378:metabolism*; D007700:Kinetics; D010649:Phenylalanine / Q000378:metabolism*; D012964:Sodium / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000470:Alkaloids; D002352:Carrier Proteins; D010649:Phenylalanine; D012964:Sodium; D006246:Harmaline