IBMX (Methylisobutylxanthine) is a broad-spectrum phosphodiesterase (PDE) inhibitor with inhibitory activity against PDE3, PDE4, and PDE5 (IC50=6.5/26.3/31.7 μM). IBMX enhances the intracellular cAMP level.

METHODS: CCDs isolated from HK-fed rats were pretreated with IBMX (100 μM) for 20 min and examined the effect of ANG II or cGMP on channel activity.
RESULTS: IBMX activated ROMK channels and prevented further channel activation by ANG II. [1]
METHODS: Primary cultures of guinea pig TSMC were assayed for the effect of KMUP-1 on cAMP and cGMP levels in the presence of IBMX (100 μM).
RESULTS: IBMX and KMUP-1 significantly increased cAMP and cGMP levels. The effect of KMUP-1 alone on cAMP and cGMP levels was not significantly different from that in the presence of IBMX. [2]
METHODS: Mammalian cell CHO was treated with IBMX (10-1000 μM) and whole cell currents were measured using the membrane clamp technique.
RESULTS: A steady-state dose-response curve for the effect of IBMX on THIK-1 currents could be fitted with a Hill coefficient of 1 and an IC50 of 120 μM.[3]

METHODS: To test the metabolic effects on mice, IBMX (1 mg/kg) was injected subcutaneously into mice twice daily for seven days.
RESULTS: IBMX significantly increased blood glucose levels in mice (blood glucose, mg/dl, control=141, IBMX=210). [4]
METHODS: To test the metabolic effects on hyperglycemic mice, glucose (0.5 g/kg) and IBMX (1 mg/kg) were injected i.v. in femoral veins into Wistar rats.
RESULTS: In hyperglycemic rats, IBMX lowered blood glucose, IBMX did not change plasma insulin levels, and IBMX decreased hepatic glycogen stores. [4]

Intracellular cyclic GMP and cyclic AMP concentrations in guinea-pig TSMCs were assayed as previously described. In brief, cells were grown in 24-well plates 10^5 cells per well. At confluence, monolayer cells were washed with phosphate buffer solution (PBS) and then incubated with KMUP-1 (0.1–100 μM) in the presence of 100 μM IBMX for 20 min. Incubation was terminated by the addition of 10% trichloroacetic acid (TCA). Cell suspensions were sonicated and then centrifuged at 2500 × g for 15 min at 4°C. To remove TCA, the supernatants were extracted three times with 5 volumes of water-saturated diethyl ether. Then, the supernatants were lyophilized and the cyclic GMP or AMP of each sample was determined by using commercially available radioimmunoassay kits [1].

Male mice (25-35 g), obtained from the animal house of Faculty of Medicine, were kept in controlled environmental conditions (temperature: 23±2 oC; light-dark cycle: 7 a.m. to 7 p.m.) and were divided randomly into groups of seven. All test compounds were dissolved in DMSO and diluted to desired concentration with less than 1% DMSO. For the experiment, the test compound (IBMX, milrinone, MCPIP, mc1, mc2, mc5 or mc6) or solvent (control) was injected subcutaneously to mice at 1 mg/kg dosage twice a day (8:00 a.m. and 8:00 p.m.) for 7 days. On day 8, animals were anesthetized with intraperitoneal injection of thiopental (80 mg/kg) and blood samples were obtained from their hearts and then the liver was dissected. Each sample was centrifuged for 5 min and its serum was separated [3].