Effect of rolipram on muscarinic acetylcholine receptor binding in the intact mouse brain

Summary.

The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE₄) and elevating cyclic AMP (cAMP), on in vivo and in vitro ³H-N-methylpiperidyl benzilate (³H-NMPB) binding to muscarinic acetylcholine receptors in the mouse brain was examined. Rolipram significantly decreased in vivo ³H-NMPB binding in the cerebral cortex, hippocampus and striatum, whereas in vitro ³H-NMPB binding in these regions was not altered. Saturation experiments on in vivo binding in conjunction with the kinetic analysis revealed that the apparent association rate constant (k_on) of ³H-NMPB binding in vivo was significantly decreased by rolipram. A similar decrease in the apparent association rate constant (k_on) by rolipram was reported for dopamine D₁ and D₂ receptor binding in vivo. These results indicate that rolipram plays an important role in the global modulation of apparent rates of ligand-receptor interactions in the intact brain.