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Abstract
GTP is one of the major cellular molecules involved in fundamental functions of cell life. Ribavirin, an antiviral and antitumoral agent, the primary site of action of which is the IMP deshydrogenase, was used in order to depress the intracellular GTP level. Consequential effects were tested on the property and dynamic of the VIP receptor on human melanoma IGR 39 cells. A concentration of 100 μM of Ribavirin reduced the intracellular GTP level by more than 60% and induced a reversible growth arrest. Nevertheless this drug displayed no effect on: i) the VIP binding parameters (Kd and Bmax) of both high and low affinity receptors; ii) the cycling of the VIP receptor; iii) the basal and VIP-stimulated cAMP production and iv) the subcellular GTP distribution. We show that Ribavirin, in the range of concentrations used, is very efficient to inhibit GTP synthesis in the human melanoma cell line IGR 39 and its growth, without affecting VIP receptor functions.