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

Thrombin rapidly induces the formation of labeled phosphatidic acid from platelets prelabeled with [17C]arachidonate or 32PO34- and specifically decreases by 50--75% the content of phosphatidylinositol. Ionophore A23187 also stimulates phosphatidate labeling, but less effectively than thrombin. This effect on phosphatidic acid is blocked by increasing the levels of cyclic AMP by preincubation with dibutyryl cyclic AMP, cyclic AMP-phosphodiesterase inhibitors or prostacyclin. Indomethacin and eicosatetraynoic acid do not alter the production of phosphatidate, indicating independence from cyclooxygenase or lipoxygenase products. Increased turnover of [14C]- or [32P]phosphatidate occurs within 2--5 s after platelet activation by thrombin and is observed before endogenous, 14C-labeled arachidonate can be detected. The rate of phosphatidate formation parallels the induced rate of serotonin release. Release of [3H]serotonin is not affected by eicosatetraynoic acid. Phosphatidate production reflects the generation of diacylglycerol by C-type phospholipase degradation of phosphatidylinositol. Diacylglycerol and phosphatidic acid may participate in the membrane modification related to the early changes in platelet shape, release reactions or aggregation which occur on stimulation.
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PMID:Stimulation of phosphatidic acid production in platelets precedes the formation of arachidonate and parallels the release of serotonin. 37 88

The modulatory effect of Ca on [Arg8]vasopressin-dependent (AVP) cAMP metabolism was studied in medullary collecting tubules (MCT) and medullary ascending limbs (MAL) microdissected from rat kidney. In MCT segments incubated in vitro with AVP, the accumulation of cAMP was enhanced (delta +59%) when Ca was omitted from the incubation medium compared with a medium with 2 mM of ionized calcium (Ca2+). Ionophore A23187 caused a decrease in AVP-stimulated cAMP accumulation in MCT in the presence of 2 mM Ca2+ but not in a Ca2+-free medium. Diltiazem and verapamil enhanced the AVP-stimulated cAMP accumulation in MCT; PTH had no detectable effect. A23187 caused a dose-dependent inhibition of cAMP accumulation stimulated by AVP with forskolin in both MCT and in MAL. However, in MAL the A23187 concentration needed for half-maximum inhibition (6.3 X 10(-6) M) was higher than for MCT (3.9 X 10(-7) M). The maximum inhibition in MAL (-65%) was less than in MCT (-97%). In the presence of 3-isobutyl-1-methylxanthine, AVP-stimulated cAMP accumulation was inhibited by A23187 in MCT (-45%) but not in MAL. Naproxen or ibuprofen did not relieve the inhibitory action of A23187 in MCT. Added Ca2+ inhibited the AVP-stimulated adenylate cyclase in MCT and MAL (half-maximum approximately equal to 5 X 10(-4) M Ca2+) and stimulated cAMP phosphodiesterase (cAMP-PDIE) in both MCT and in MAL (half-maximum approximately equal to 9 X 10(-5) M Ca2+). Incubation of MCT and MAL with A23187 decreased (-50%) the content of ATP. Results suggest that increased influx of extracellular Ca2+ inhibits the AVP-stimulated cAMP accumulation in MCT and to a much lesser degree in MAL. Deceased cAMP accumulation in MCT is probably due to both stimulation of cAMP-PDIE and the inhibition of adenylate cyclase, whereas in MAL it is due to stimulation of cAMP-PDIE. The results suggest that Ca2+ influx exhibits a negative modulatory effect on AVP-dependent cAMP metabolism mainly in MCT.
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PMID:Effects of calcium on the vasopressin-sensitive cAMP metabolism in medullary tubules. 241 23

The inositol phospholipids of peritoneal macrophages were prelabeled with [3H]inositol to enable studies on the enzymatic mechanisms of stimulus-induced phosphatidylinositol breakdown. Ionophore A23187 induced a rapid breakdown of phosphatidylinositol in the presence of Ca2+ with 25% loss occurring within 5 min. The main water-soluble product of this breakdown was identified as inositol diphosphate. Since the accumulation of inositol diphosphate far exceeded the concomitant decrease in polyphosphoinositides, an increased phosphorylation of phosphatidylinositol must have preceded, or accompanied, the degradation of diphosphoinositide. The degradation of phosphatidylinositol induced by A23187 was shown to be strictly dependent on Ca2+. The monovalent cation ionophore monensin and platelet-activating factor increased the level of diphosphoinositide but caused no net degradation of inositol phospholipids. The same effect was seen with ionophore A23187 in the absence of Ca2+. Zymosan particles also induced extensive degradation of phosphatidylinositol. Products of phosphodiesterase-catalyzed cleavage of inositol lipids were observed, but the pathway of deacylation dominated as evidenced by the accumulation of lysophosphatidylinositol and glycerophosphoinositol. Deacylation was also enhanced in response to concanavalin A. Thus, in mouse peritoneal macrophages phosphatidylinositol breakdown occurred primarily by deacylation or via diphosphoinositide, depending on the stimulus, rather than through a phosphatidylinositol phosphodiesterase reaction.
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PMID:Differential activation of phosphatidylinositol deacylation and a pathway via diphosphoinositide in macrophages responding to zymosan and ionophore A23187. 632 96