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 activity of cAMP and cGMP phosphodiesterases in the cytosol and endoplasmic reticulum fraction of rat adipocytes was studied in animals of 4 groups: intact and adrenalectomized rats with normal pressure, intact and adrenalectmized rats with spontaneous genetic hypertension. It is shown that in animals of all groups the rate of cGMP hydrolysis in these fractions is higher than the rate of cAMP hydrolysis and that 90% of the activity of the enzymes that were studied occurs in the cytosol. Determination of the dependence of phosphodiesterase activity of cyclic nucleoides on a substrate concentration of 10(-8) to 10(-4) M made it possible to estimate the values of Hill's coefficients characterizing the degree of co-operation of the noted reactions. Increased activity of cAMP phosphodiesterase with low and high Km value and increased activity of cGMP enzyme were revealed in the cytosol of fat cells in rats with normal pressure after removal of the adrenals; the activity of these enzymes in the endoplasmic reticulum fraction did not change after adrenalectomy. In rats with spontaneous genetic hypertension the activity of both forms of cAMP and cGMP enzymes in the adipocyte cytosol increased after removal of the adrenals; in the microsome fraction the activity of cAMP phosphodiesterase with low Km value was reduced whereas the activity of cAMP phosphodiesterase with high Km value and the activity of cGMP in the region of high substrate concentration were increased.
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PMID:[Phosphodiesterase characteristics of the fat cells in spontaneous hypertension in rats]. 625 65

This study tested the hypothesis that regulation of 3',5'-cAMP levels in the kidney vasculature is abnormal in spontaneously hypertensive rats. In isolated, perfused kidneys from adult rats (16 weeks of age), isoproterenol similarly increased renal venous 3',5'-cAMP secretion from kidneys of hypertensive versus normotensive Wistar-Kyoto rats. However, a broad-spectrum phosphodiesterase inhibitor (isobutyl-1-methylxanthine) augmented isoproterenol (3 mumol/L)-induced increases in renal venous 3',5'-cAMP secretion more so in kidneys from adult hypertensive versus age-matched normotensive rats (31-fold and 5-fold, respectively; P<0.0001). In contrast to isoproterenol, broad-spectrum phosphodiesterase inhibition augmented forskolin-induced increases in renal venous 3',5'-cAMP secretion similarly in kidneys from adult hypertensive versus age-matched normotensive rats. In kidneys from adults of both strains, the effects of isobutyl-1-methylxanthine on isoproterenol-induced 3',5'-cAMP responses were mimicked by the inhibition of phosphodiesterase 4 (RO 20-1724) but not by the inhibition of phosphodiesterase 1 (3,8-methoxymethyl-3-isobutyl-1-methylxanthine) or phosphodiesterase 3 (milrinone). In kidneys from young (5 weeks of age), adult, and old (39 weeks of age) rats, RO 20-1724 augmented isoproterenol-induced renal 3',5'-cAMP secretion more so in kidneys from hypertensive rats. In adult hypertensive rats, arterial blood pressure and renal vascular resistance were elevated compared with age-matched normotensive rats, and intravenous infusions of RO 20-1724 reduced blood pressure and renal vascular resistance in hypertensive rats but had little effect on these variables in normotensive rats. We conclude that, in the renal vasculature of spontaneously hypertensive rats (young, adult, and old), there is increased activity of a compartment of phosphodiesterase 4. Selective inhibition of renal vascular phosphodiesterase 4 may represent a new strategy for improving renal hemodynamics in genetic hypertension.
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PMID:Regulation of renovascular adenosine 3',5'-cyclic monophosphate in spontaneously hypertensive rats. 1952 65