Cyclic nucleotide phosphodiesterase (PDE), that is a multigenic enzyme superfamily ubiquitously distributed in mammalians, mainly contributes to intracellular signaling regulation. Its various isozymes specifically control in a spatio-temporal manner intracellular levels of cAMP and cGMP downstream receptor activation and nearby functional proteins[1].The compound ICI 63197, a selective inhibitor of the peripheral plasma membrane phosphodiesterase(PDE).[2]. ICI 63,197 and levodopa produced isoprenaline-like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated[3].ICI 63 197 (10 umol/l, 10 rnin incubation) increased cyclic AMP level by 29-39% in 3 preparations but decreased the level by 6% in one other preparation. Mean levels increased significantly (P<0.05, n =4). There was no consistent change in cyclic GMP level which
decreased up to 47% or increased up to 15%. A higher dose of ICI 63 197 (50 umol/l,10 rnin incubation) increased cyclic AMP levels by 17-281%. The mean increase was statistically significant (P<0.01, n=4). As with the lower dose of ICI 63 197, there was no consistent change in cyclic GMP level which decreased up to 29% or increased up to 46%[4].While pretreatment with a single dose of rolipram, ICI 63,197 or IBMX administered either 1 or 24 h prior to clonidine (0.1 mg/kg) enhanced clonidine-induced hypothermia and hypoactivity, chronic dosing (twice daily for 14 days) with desipramine (10 mg/kg) or rolipram (5 mg/kg) antagonized these behavioural effects. In contrast, chronic dosing with IBMX or ICI 63,197 failed to antagonize clonidine-induced hypothermia and hypoactivity[5].
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