The effects of ribavirin on the GTP level and the VIP receptor dynamic of human IGR39 cells.
GTP is one of the major cellular molecules involved in fundamental functions of cell life. Ribavirin, and 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 microM of Ribavirin reduced the intracelluar 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 based 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.
Fouchier
F
F
Laboratoire Biochimie Cellulaire-URA CNRS 1924, Faculté de Pharmacie, Marseille, France.
Forget
P
P
Bellan
C
C
Marvaldi
J
J
Champion
S
S
Pichon
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects / Q000378:metabolism*; D012254:Ribavirin / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D018005:Receptors, Vasoactive Intestinal Peptide; D006165:Guanylyl Imidodiphosphate; D014660:Vasoactive Intestinal Peptide; D012254:Ribavirin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate