The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat.
The effects of selective and non-selective 3',5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors on cGMP and cAMP accumulation were studied in rat hippocampal slices incubated in vitro. The following PDE inhibitors were used: vinpocetine and calmidazolium (PDE1 selective), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, PDE2 selective), SK&F 95654 (PDE3 selective), rolipram (PDE4 selective), SK&F 96231 (PDE5 selective), the mixed type inhibitors zaprinast and dipyridamole, and the non-selective inhibitors 3-isobutyl-1-metylxanthine (IBMX) and caffeine. cGMP levels were increased in the presence of different concentrations of IBMX, EHNA, dipyridamole, vinpocetine and rolipram. cGMP immunocytochemistry showed that incubation with different inhibitors in the presence and/or absence of sodium nitroprusside resulted in pronounced differences in the extent and regional localization of the cGMP response and indicate that PDE activity in the hippocampus is high and diverse in nature. The results suggest an interaction between cGMP and cAMP signalling pathways in astrocytes of the rat hippocampus.
van Staveren WC
Maastricht University, Department of Psychiatry and Neuropsychology, Universiteitssingel 50, POB 616, 6200 MD, Maastricht, The Netherlands. w.vanstaveren@np.unimaas.nl
Markerink-van Ittersum M
Steinbusch
H W
HW
de Vente J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D006162:Guanylate Cyclase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D009599:Nitroprusside; D005576:Colforsin; D002110:Caffeine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine