Mechanisms of decreased cerebrospinal fluid production by radiographic contrast media: role of adenylate cyclase activation

PP Harnish, FK Northington, V DiStefano and S Banerjee

The i.v. administration of radiographic contrast media decreases cerebrospinal fluid (CSF) production as measured by negative pressure collection from the lateral ventricles of anesthetized dogs. Evidence suggests that adrenergic-mediated adenylate cyclase (AC) activity controls CSF production. AC activity was measured in membrane fractions of bovine and canine choroid plexus and rat heart and lung in the presence of various concentrations of the contrast agent sodium diatrizoate. A concentration-dependent inhibition of isoproterenol- stimulated AC activity by the contrast agent was observed in vitro. Specific binding of [3H]dihydroalprenolol to membrane fractions of bovine choroid plexus was also inhibited by sodium diatrizoate. An indication that the inhibition of choroidal AC activity by contrast media is significant in vivo was obtained by measuring CSF production in dogs. The inhibition of CSF production by sodium diatrizoate was reduced 50% when the contrast agent was administered during an i.v. infusion of isoproterenol (100 ng/kg/min). These results indicate that the mechanism of decreased CSF production by contrast media may involve inhibition of beta adrenergic-stimulated AC activity.

Volume 236, Issue 2, pp. 464-469, 02/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics