Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behavioral effects of 3-isobutyl-1-methylxanthine (IBMX) were compared with those of caffeine and 7-(2-chloroethyl) theophylline (7-CET) in squirrel monkeys under a multiple schedule of reinforcement in which fixed-interval responding was maintained alternately by presentation of food and presentation of electric shock. All three drugs produced dose-related increases in response rate in both components of the multiple schedule. Thus, although IBMX generally lacks psychomotor-stimulant effects in rodents, it had behavioral effects in squirrel monkeys that were qualitatively similar to those of caffeine. Based on the average ED50 values, IBMX was 5-7 times more potent than caffeine and 7-CET was twice as potent as caffeine in the two schedule components. This potency relation corresponds well with those observed in radioligand binding assays for central adenosine receptors and is consistent with the view that the psychomotor-stimulant effects of methylxanthines are linked to their antagonistic actions at the adenosine-receptor level. There was no obvious correspondence between the capacity of the methylxanthines to increase response rate and their capacity to inhibit phosphodiesterase activity.
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PMID:Psychomotor-stimulant effects of 3-isobutyl-1-methylxanthine: comparison with caffeine and 7-(2-chloroethyl) theophylline. 248 86

1. The lungs of two groups of lambs aged 0-2 weeks and 6-12 weeks were artificially perfused in situ with warmed and oxygenated sheep blood. The airspaces of the lungs were filled with liquid containing an impermeant tracer to allow estimation of net liquid movement across the pulmonary epithelium at rest and after administration of certain drugs. 2. Dibutyryl cAMP (dB-cAMP, 10-4 M) stimulated the rate of lung liquid (LL) absorption in the lungs of four neonatal sheep aged 9-12 days, from -1.43 +/- 0.2 to -2.75 +/- 0.3 ml h-1 (kg body wt)-1 (P < 0.05, comparison of regression lines by Student's t test), but had no effect in four juvenile sheep aged 6-12 weeks (P > 0.10). 3. Theophylline, a non-selective phosphodiesterase (PDE) inhibitor (5 x 10-4 M), increased LL absorption from a resting rate of -1.55 +/- 0.3 to -3.62 +/- 0.5 ml h-1 kg-1 in the lungs of four sheep aged 1-12 days and from -1.47 +/- 0.3 to -3.73 +/- 0.4 ml h-1 kg-1 in four sheep aged 6-12 weeks (P < 0.05, Student's paired t test). 4. The beta-adrenergic antagonist sotalol (10-4 M) reduced LL absorption rate from -1.47 +/- 0.1 to -1.22 +/- 0.1 ml h-1 kg-1 (P < 0.01) in the lungs of four sheep aged 4-13 days, while theophylline given after sotalol had no effect. In four sheep aged 6-12 weeks, sotalol had no effect on LL absorption rate, whereas theophylline given after sotalol increased LL absorption rate from -1.06 +/- 0.1 to -1.92 +/- 0.2 ml h-1 kg-1 (P < 0.05). 5. The A1/A2 purinergic receptor blocker 7-(beta-chloroethyl) theophylline (CET; given at 5 x 10-6 M and 10-4 M) had no effect on LL absorption rate in the lungs of four sheep aged 6-12 weeks, confirming that theophylline produced its effect of increasing LL absorption by inhibiting PDE hydrolytic activity. 6. The selective PDE IV (cAMP-specific) PDE inhibitor rolipram was given in the perfused lungs of seven sheep aged 6-12 weeks at doses between 10-8 and 10-4 M, increasing LL absorption rate at concentrations of 10-6 M and above; the half-maximal effective concentration was estimated to be 5.9 x 10-7 M. 7. Rolipram (10-5 M) increased LL absorption rate from -1.99 +/- 0.2 to -3.18 +/- 0.5 ml h-1 kg-1 in the perfused lungs of four sheep aged 6-11 days, and from -1.21 +/- 0.4 to -3.45 +/- 0.3 ml h-1 kg-1 in the perfused lungs of four sheep aged 6-12 weeks (P < 0.05). Sotalol (10-4 M) reduced LL absorption rate from -3.39 +/- 0.8 to -2. 18 +/- 0.4 ml h-1 kg-1 (P < 0.05) in four sheep aged 10-14 days, while rolipram given after sotalol had no effect. In four sheep aged 6-12 weeks, sotalol had no effect on resting LL absorption rate, whereas rolipram given after sotalol increased absorption rate from -1.27 +/- 0.1 to -2.02 +/- 0.6 ml h-1 kg-1 (P < 0.05). 8. We conclude that cAMP mediates a component of LL absorption postnatally, and that while beta-adrenergic stimulation was the sole source of endogenous cAMP in neonates, this was not the case in juveniles, in whom cAMP originated, at least in part, from other sources.
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PMID:The regulation of lung liquid absorption by endogenous cAMP in postnatal sheep lungs perfused in situ. 970 33