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Iohexol inhibits adenylate cyclase
P P Harnish1, F K Northington, K A Samuel
1Department of Radiology, University of Rochester Medical Center, New York 14642.
Insights
Radiographic contrast agents like iohexol reduce cerebrospinal fluid (CSF) production by inhibiting adenylate cyclase (AC) activity. This enzyme plays a key role in regulating CSF formation.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Intravenous administration of radiographic contrast agents, including diatrizoate and iohexol, has been shown to decrease cerebrospinal fluid (CSF) production.
- Adrenergic-mediated adenylate cyclase (AC) activity is implicated in the control of CSF production.
- Previous research indicated that diatrizoate inhibits AC activity.
Purpose of the Study:
- To investigate the effect of the nonionic contrast agent iohexol on adenylate cyclase (AC) activity.
- To determine if iohexol, similar to diatrizoate, inhibits AC activity involved in CSF production.
Main Methods:
- Adenylate cyclase (AC) activity was measured in membrane fractions isolated from bovine choroid plexus.
- The enzyme activity was assessed in the presence of varying concentrations of iohexol.
- Both basal and adrenergic-stimulated AC activity were evaluated.
Main Results:
- Iohexol demonstrated a concentration-dependent inhibition of both basal and adrenergic-stimulated AC activity.
- The concentration of iohexol required for 50% inhibition of AC activity was approximately 2.3 mM.
- This inhibitory concentration is comparable to that observed for diatrizoate.
Conclusions:
- Iohexol inhibits adenylate cyclase (AC) activity in the bovine choroid plexus.
- This inhibition of AC activity by iohexol provides a potential mechanism for the observed reduction in CSF production.
- Contrast media may reduce CSF production through the inhibition of AC activity.
Abstract:
Previous studies demonstrated that the intravenous administration of the ionic radiographic contrast agent, diatrizoate, and the nonionic agent, iohexol, causes a decrease in the rate of cerebrospinal fluid (CSF) production. Evidence suggests that adrenergic-mediated adenylate cyclase (AC) activity controls CSF production. Diatrizoate was found to inhibit AC activity. The authors now report that iohexol inhibits activity of this enzyme. Adenylate cyclase activity was measured in membrane fractions of bovine choroid plexus in the presence of various concentrations of iohexol. A concentration-dependent inhibition of basal and adrenergic-stimulated AC activity by the contrast agent was observed. The concentration of iohexol that produced a 50% inhibition was about 2.3 mM. This is similar to the concentration of diatrizoate that produced equivalent enzyme inhibition. These results support the contention that one mechanism for the action of contrast media in reducing CSF production involves inhibition of AC activity.