Reduction in β‐Adrenergic Response of Cultured Glioma Cells Following Depletion of Intracellular GTP

• Published in: European journal of biochemistry Vol. 77; no. 1; pp. 113 - 117
• Main Authors: FRANKLIN, Trevor J., TWOSE, Patricia A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1977
• Subjects: Adenosine Triphosphate - metabolism; Adenylyl Cyclases - metabolism; Cell Line; Cell Membrane - drug effects; Cell Membrane - enzymology; Cyclic AMP - metabolism; Enzyme Activation; Glioma - metabolism; Guanosine Triphosphate - metabolism; Guanosine Triphosphate - pharmacology; Isoproterenol - pharmacology; Kinetics; Mycophenolic Acid - pharmacology; Time Factors
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1111/j.1432-1033.1977.tb11648.x

1. When C6 glioma cells were incubated with mycophenolic acid, a potent and specific inhibitor of IMP:NAD oxidoreductase (EC 1.2.1.14) there was a marked depletion of the cellular content of GTP. The viability of the cells was unaffected. 2. The adenosine 3′:5′‐monophosphate (cyclic AMP) response of C6 glioma cells to the β‐adrenergic stimulant, (±)isoprenaline, was considerably reduced after treatment with mycophenolic acid. The diminished response to (±)isoprenaline was prevented by the inclusion of guanine in the culture medium along with mycophenolic acid. 3. The adenylate cyclase response to (±)isoprenaline of whole homogenates from C6 cells treated with mycophenolic acid was also depressed; the response was restored to normal by the addition of GTP. 4. The adenylate cyclase response to (±)isoprenaline of a membrane fraction prepared from homogenates of C6 cells was almost totally dependent on the presence of added GTP. Membrane fractions from control and mycophenolic‐acid‐treated C6 cells gave similar adenylate cyclase responses to (±)isoprenaline in the presence of GTP. 5. It is concluded that mycophenolic acid may depress the β‐adrenergic sensitivity of C6 cells by depleting the cellular content of GTP.