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

TY - JOUR

T1 - Effect of rolipram on muscarinic acetylcholine receptor binding in the intact mouse brain

AU - Hosoi, R

AU - Ishikawa, M

AU - Kobayashi, K

AU - Gee, A

AU - Yamaguchi, M

AU - Inoue, O

PY - 2003/4

Y1 - 2003/4

N2 - The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE4) and elevating cyclic AMP (CAMP), on in vivo and in vitro H-3-N-methylpiperidyl benzilate (H-3-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 H-3-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 D-1 and D-2 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.

AB - The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE4) and elevating cyclic AMP (CAMP), on in vivo and in vitro H-3-N-methylpiperidyl benzilate (H-3-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 H-3-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 D-1 and D-2 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.

U2 - 10.1007/s00702-002-0797-1

DO - 10.1007/s00702-002-0797-1

M3 - Article

C2 - 12658364

SN - 0300-9564

VL - 110

SP - 363

EP - 372

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

IS - 4

ER -