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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effects of rolipram on in vivo dopamine receptor binding.

In order to clarify whether changes in brain concentrations of the second messenger cyclic AMP (cAMP) affect in vivo receptor binding in the brain, the effects of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)), on dopamine receptor binding in the mouse brain were studied. Rolipram significantly decreased in vivo (3)H-SCH 23390 (dopamine D(1) selective radioligand) binding in the mouse striatum in a dose-dependent manner. In vivo saturation experiments together with the kinetic analysis of (3)H-SCH 23390 binding revealed that the apparent association rate constant (k(on)) for (3)H-SCH 23390 binding rather than the maximum number of binding sites available (B(max)) was decreased by rolipram. (3)H-N-methylspiperone (NMSP, dopamine D(2) selective radioligand) binding in the mouse striatum was also decreased by rolipram whereas no significant changes in (3)H-raclopride (dopamine D(2) selective radioligand) binding were observed. As (3)H-raclopride binding has been reported to be much more sensitive than (3)H-NMSP binding to competition by endogenous dopamine, the decreases in (3)H-SCH 23390 and (3)H-NMSP binding cannot be attributed to competitive inhibition by endogenous dopamine. These results indicate that changes in second messenger cAMP concentrations may affect the apparent bimolecular association rate constant (k(on)) of dopamine receptor binding in intact brain. This may be mediated by changes in the receptor micro-environment and altered actual free ligand concentration surrounding the receptors.[1]

References

  1. Effects of rolipram on in vivo dopamine receptor binding. Hosoi, R., Ishikawa, M., Kobayashi, K., Gee, A., Yamaguchi, M., Inoue, O. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
 
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