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)

The differentiation of rat liver lysosomal acid phosphatase, acid ATPase, acid phosphodiesterase, acid ribonuclease, and acid deoxyribonuclease was studied by isoelectric focusing. To prevent autolytic digestion, inhibitors of cathepsins and neuraminidase were used. The proportion of acidic forms of acid phosphatase, acid ATPase and acid phosphodiesterase was increased by the use of extraction medium containing 0.05% Triton X-100. To investigate the identity of acid ATPase and acid phosphodiesterase, the relative activities among the multiple forms of these enzymes, the acid phosphodiesterase/acid ATPase ratio at each activity peak, and the degree of enzyme inhibition by p-chloromercuriphenyl sulfonic acid were estimated. The results suggest that acid ATPase is not identical with acid phosphodiesterase. With extraction medium free of Triton X-100, acid ribonuclease appeared in two forms. However, in addition to these forms, a new form of this enzyme with a more acidic pI (4.22) emerged when extraction medium containing 0.05% Triton X-100 was used. The major peak of acid deoxyribonuclease with pI=8.40-9.39 was obtained regardless of the extracting method.
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PMID:An isoelectric focusing study of acid phosphohydrolases in rat liver lysosomes. 2 87

We have perfused isolated rat livers with hypocalcemic (4.4 mg 100 ml) Krebs-Ringer bicarbonate albumin buffer. After 15 min of perfusion, a substance appeared in the perfusate which decreased rat renal adenylate cyclase activation by parathyroid hormone (PTH). The material in the perfusate was purified greater than 50,000-fold by Bio-Gel P-10 chromatography. The purified antagonist decreased the activation of rat renal cortical adenylate cyclase by PTH, glucagon, and epinephrine 75 to 100%. Concentration response curves for each of the hormones indicated a noncompetitive interaction of the inhibitor with the hormone. The inhibition was not species-specific, as the activation of the parathyroid hormone-responsive adenylate cyclase in cat renal cortex was also abolished by the inhibitor from the perfused rat liver. The inhibitor is a peptide, Mr equal to similar to 1000, which is heat-stable, acid-stable, alkai-labile, and is destroyed by trypsin, leucine aminopeptidase, and elastase. It is not destroyed by phosphodiesterase, 5'-nucleotidase, alkaline phosphatase, neuraminidase, RNase, or phospholipase A. The inhibitor is not produced by isolated rat livers perfused with normocalcemic perfusion media. It is unclear whether the peptide is synthesized by the liver or whether it is a breakdown product of a larger peptide or protein in the liver. This is the first reported peptide inhibitor of adenylate cyclase.
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PMID:Isolation of a unique peptide inhibitor of hormone-responsive adenylate cyclase. 16 24

This report focuses on two groups of cationic cancerostatics, anthracycline antibiotics and 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone), lining up biophysical and biochemical effects on the level of membranes and membrane constituents. The interaction of both drugs with multilamellar liposomes consisting of phosphatidylcholine used as a simple model membrane system could be ensured by means of steady state and nanosecond time-resolved fluorometric investigations. The biochemical effect on membranes is underlined by the inhibition of the neuraminidase activity of the Sendai virus, modification of the CAMP phosphodiesterase activity of leukemia L 1210 cells of mice and reduction of the lymphocyte blast transformation.
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PMID:Cationic anticancer drugs and their modes of action. 256 92

An in vitro bioassay based on progesterone production by enzymatically-dispersed immature rat ovary cells, was used to investigate the effect of sialidase treatment on the biological activity of human chorionic gonadotrophin (hCG). The potency in this bioassay system and in an ovarian receptor assay were compared, to substantiate possible discrepancies between the effect of this treatment on biological activity and on receptor binding. Ovarian cells responded dose-dependently to the addition of hCG as well as sialidase treated hCG (asialo-hCG). Dose-response curves of hCG and asialo-hCG were parallel and the maximal stimulation levels reached were the same. Sub-maximal doses of hCG and asialo-hCG were additive. The potency of asialo-hCG was 65% of the original preparation. Addition of low concentrations of phosphodiesterase inhibitor resulted in a greatly enhanced sensitivity of the bioassay, but had no effect on the potencies of asialo-hCG and hCG. In contrast to intact gonadotrophins, the receptor assay potency of asialo-hCG was more than three times the bioassay potency. In agreement with this, it was found that when equal amounts of 125I-labelled hCG and asialo-hCG were specifically bound to the ovarian cells, the latter stimulated progesterone production less effectively. It is concluded that there is a discrepancy between the effect of desialylation on the biological activity and on the receptor-binding ability of hCG.
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PMID:Discrepancy between the effects of desialylation of human chorionic gonadotrophin on in vitro ovarian biological activity and on receptor binding. 625 8

The 10 S DNA polymerase alpha from calf thymus (Masaki, S., and Yoshida, S. (1978) Biochim. Biophys. Acta 521, 74-88) has been purified to near homogeneity. The most purified fraction obtained by repeated sucrose rate-zonal centrifugation contained three large polypeptides of 150,000, 145,000, and 140,000 daltons and three to four smaller polypeptides ranging from 43,000 to 50,000 daltons. A good resolution of these polypeptides was achieved on a sodium dodecyl sulfate-polyacrylamide linear gradient gel (5-20%) which was stained by the silver stain method. The three large polypeptides were also observed in the more crude fractions prepared in the presence of three kinds of protease inhibitors. By a peptide mapping analysis, it was revealed that these three polypeptides have a similar primary structure. Treatments of the enzyme with alkaline phosphatase, phosphodiesterase, and neuraminidase did not affect the gel pattern. These results indicate that the 10 S DNA polymerase alpha of calf thymus has a microheterogeneity in terms of the large polypeptide component. Among these three large polypeptides, the two polypeptides of 150,000 and 145,000 daltons disappeared by keeping the sucrose gradient fraction at 4 degrees C in the absence of glycerol, while the 140,000-dalton polypeptide was well preserved. The poly(rA)oligo(dT)-dependent activity of 10 S DNA polymerase alpha was selectively lost under this condition.
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PMID:10 S DNA polymerase alpha of calf thymus shows a microheterogeneity in its large polypeptide component. 708 21

Adriamycin (ADR) induces nonimmunological and noncytotoxic histamine release from peritoneal and pleural rat mast cells. This secretion is unaffected by the pretreatment with pertussis toxin, cholera toxin and benzalkonium chloride. Histamine release induced by compound 48/80, was markedly inhibited by pertussis toxin, cholera toxin, benzalkonium chloride and neuraminidase. The ADR dose-response curve is significantly shifted to the right when cells were preincubated with the unspecific phosphodiesterase inhibitor IBMX. The activation of protein kinase C (PKC) with the phorbol esther TPA increases the response to ADR, while PKC inhibition with trifluoperazine decreases histamine release. The pretreatment of mast cells with okadaic acid did not modify the response to ADR. These results suggest that ADR elicits histamine release with a mechanism notably different from compound 48/80.
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PMID:Study of the activation mechanism of adriamycin on rat mast cells. 753 76