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)

Calmodulin, a calcium-dependent modulator protein, is known to mediate a great number of Ca++-dependent processes in various tissues. Although it was originally described as a protein activator of cyclic nucleotide phosphodiesterase, the sensitivity of phosphodiesterases to this compound are suggested to be variable from tissue to tissue. In order to determine whether there was calmodulin-like activity in pig skin epidermis and to see its relationship to epidermal phosphodiesterase, we used an established calmodulin deficient phosphodiesterase system prepared from bovine heart. Calmodulin deficient phosphodiesterase prepared from bovine heart was markedly stimulated by the addition of pig skin (epidermal) boiled extract in the presence of calcium. Boiled skin extract alone had only little phosphodiesterase activity by itself. This effect of boiled skin extract on bovine heart phosphodiesterase was inhibited by the addition of EGTA, a divalent metal ion chelator of relative Ca++ specificity. At a fixed concentration of EGTA, increasing the Ca++ concentration counteracted the effect of EGTA. Pure pig skin epidermis (separated by trypsinization, NaBr, CaCl2-sucrose or NH4Cl treatment) was also shown to have heat-stable calmodulin activity. In contrast to the bovine heart phosphodiesterase, epidermal phosphodiesterase was only partially inhibited when Ca++ was removed by EGTA. The addition of boiled skin extract on the crude extract of epidermal phosphodiesterase had minimal effect on the enzyme activity. Overall results indicate that although pig skin epidermis contains significant amount of calmodulin, the regulation of phosphodiesterase may not be the main biological activity of epidermal calmodulin.
J Invest Dermatol 1982 Mar
PMID:Pig skin epidermal calmodulin: effect on calmodulin deficient phosphodiesterase. 627 75

Peripheral blood lymphocyte cyclic AMP responses to isoprenaline, prostaglandin E2 and histamine were examined in patients with atopic eczema, in the presence and absence of a potent phosphodiesterase inhibitor (PDEI). Basal cyclic AMP levels were not significantly different in atopic and control groups. In the presence of the PDEI, there were impaired cyclic AMP responses to both isoprenaline and prostaglandin E2 in the atopic group. Differences between atopic and control cyclic AMP responses were exaggerated by the omission of the PDEI, when impaired responses to all agonists were observed in lymphocytes from atopic subjects. These results imply that, in atopic eczema, lymphocytes exhibit impaired responses not only at the beta-adrenoceptor site but at unrelated sites of adenylate cyclase activation, and these observations are consistent with increased leukocyte phosphodiesterase activity.
Br J Dermatol 1983 Nov
PMID:Impaired lymphocyte cyclic adenosine monophosphate responses in atopic eczema. 631 45

It has been reported that pig skin epidermis contains at least four independent adenylate cyclase systems, i.e. 1) beta-adrenergic-, 2) histamine H2-, 3) adenosine and, 4) prostaglandin E-adenylate cyclase systems, resulting in the accumulation of cyclic AMP. Using human skin epidermis, we investigated the responses of adenylate cyclase to epinephrine, histamine, and adenosine. In normal human skin, all three agents increased cyclic AMP levels of the skin. The epinephrine effect was inhibited by a beta-adrenergic blocking agent, propranolol. The histamine effect was inhibited by a histamine H2 inhibitor, cimetidine. The adenosine effect was inhibited by theophylline. The effects of epinephrine and histamine were augmented by the addition of the cyclic AMP phosphodiesterase inhibitor, theophylline. Another phosphodiesterase inhibitor, papaverine, augmented the effects of all three agents. In contrast to pig skin epidermis, where histamine and adenosine-induced cyclic AMP accumulations were marked, in human skin, epinephrine-induced cyclic AMP accumulation was more marked than those induced by histamine and adenosine. Using the epidermis of Darier's disease, we also investigated the effects of epinephrine, histamine and adenosine on the cyclic AMP levels of the skin. The involved skin of Darier's disease was shown to be characterized by a defective beta-adrenergic responsiveness. These findings show that normal human skin possesses at least three independent adenylate cyclase systems (beta-adrenergic, histamine H2-, and adenosine-adenylate cyclase), as in pig skin epidermis, with a different responsiveness pattern to these stimulators. Our data also show that the responsiveness to each receptor-adenylate cyclase system may be modified in a pathological condition of epidermis such as in Darier's disease. The significance of decreased beta-adrenergic responsiveness in the involved skin in Darier's disease was discussed in relation to our previous finding of the same type of defect in the psoriatic-involved epidermis.
Curr Probl Dermatol 1983
PMID:Human skin epidermal adenylate cyclase systems: defective beta-adrenergic responsiveness in the involved epidermis of Darier's disease. 631 92

The aim of this study was to determine whether levels of biologically active calmodulin are elevated in both lesional and uninvolved epidermis in psoriasis. Epidermal shave biopsies were obtained from normal controls and from both psoriatic plaques and nonlesional psoriatic skin. Following determination of the protein content, the calmodulin activity of the homogenized samples was then measured using a calmodulin-sensitive phosphodiesterase enzyme bioassay. In normal skin, calmodulin activity was 1.29 +/- 0.35 micrograms calmodulin mg-1 epidermal protein (mean +/- SEM, n = 12 volunteers) compared to 7.88 +/- 1.59 micrograms calmodulin mg-1 epidermal protein for plaque (n = 16 patients) and 10.19 +/- 2.35 micrograms calmodulin mg-1 epidermal protein for the uninvolved skin of 12 of these patients. The levels of biologically active calmodulin were therefore elevated in both plaque and uninvolved epidermis of patients with psoriasis compared to epidermis from normal volunteers. These results suggest that an abnormality in the regulation of calmodulin activity may be involved in the pathogenesis of psoriasis.
J Invest Dermatol 1984 Mar
PMID:Biologically active calmodulin levels are elevated in both involved and uninvolved epidermis in psoriasis. 632 4

It has been proposed that immune dysfunction in psoriasis is a consequence of aberrant cyclic nucleotide metabolism. We have examined cyclic AMP responses to isoprenaline, histamine, and prostaglandin E2 in peripheral blood mononuclear leukocytes from patients with psoriasis, in the presence and absence of a potent cyclic AMP phosphodiesterase inhibitor. Stimulated and basal cyclic AMP levels in mononuclear leukocytes from psoriatics did not differ from those observed in mononuclear leukocytes from normal subjects, irrespective of the stimulant employed, either in the presence or in the absence of the phosphodiesterase inhibitor. These findings do not support the hypothesis that psoriasis is associated with either impaired beta-adrenergic reactivity or a more generalized abnormality of mononuclear leukocyte cyclic nucleotide metabolism.
J Invest Dermatol 1984 Apr
PMID:Mononuclear leukocyte cyclic adenosine monophosphate responses in psoriasis are normal. 632 85

The effect of theophylline, an inhibitor of phosphodiesterase, on tyrosine (Tyr) transport across cell membrane was studied using cultured B-16 mouse melanoma cells. 1.5 mM Theophylline in culture medium increased Tyr uptake velocity in linear fashion up to 36 h, after which it reached a plateau at which the cells showed about a 60% increase in Tyr transport velocity. This increase was independent of extracellular Na, essentially unaffected by cell density, and partially inhibited by concomitantly added cycloheximide. These results suggested that biosynthesis of macromolecules, probably acting as System L transporter, was induced by theophylline treatment.
Arch Dermatol Res 1984
PMID:Effect of theophylline on the transport of tyrosine in cultured B-16 mouse melanoma cells. 643 10

Human epidermal calmodulin was purified by phenothiazine-Sepharose affinity chromatography. The protein stimulated activator-deficient phosphodiesterase and was identified to be calmodulin by radioimmunoassay. Epidermal calmodulin demonstrated a Mr of 17,000 on gel permeation chromatography and migrated on sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis as a single band at the same location as rat testes calmodulin. The exact role of calmodulin in the epidermis remains to be defined.
J Invest Dermatol 1983 Jul
PMID:Purification of human epidermal calmodulin. 686 82

Atopic dermatitis is a chronically relapsing inflammatory skin disease with altered immune and pharmacologic responses. Elevated serum IgE probably reflects defective immune regulation. Various other cellular immune defects rise and fall exacerbations and remissions of skin inflammation. Increased responsiveness to cholinergic and alpha adrenergic agents may relate to abnormalities of cyclic nucleotide regulation. Recent observations of abnormal cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity in atopic dermatitis may provide new insights into the pathogenesis and treatment of the disease.
J Am Acad Dermatol 1982 Jan
PMID:Atopic dermatitis. 704 69

A plasma membrane fraction from Malpighian cells has been isolated by differential and density gradient centrifugation of a pig epidermal homogenate. It was enriched in the marker enzymes 2-naphthylamidase, 5'-nucleotidase, phosphodiesterase I and acid phosphatase and depleted of NADH-ferricyanide reductase and cytochrome c oxidase. It had a protein to lipid ratio of 3:2 by weight. The protein composition was complex with compounds ranging from a molecular weight of 150,000 down to 13,000. Major components with molecular weights 120,000 to 90,000 were glycoproteins. Two other components had molecular weights of 39,000 (actin ?) and 24,000. There were minor components with molecular weights from 63,000 to 46,000. About 76% of the total lipid was present as phospholipid, which was enriched in sphingomyelin. Most of the neutral lipids were accounted for by cholesterol, triacylglycerols and fatty acids: very little glycosphingolipid was present. The preparation was probably derived from non-desmosomal areas of the plasma membrane of Malpighian cells, as desmosomes were not seen in the preparation.
Br J Dermatol 1980 Nov
PMID:The plasma membrane of Malpighian cells from pig epidermis: isolation and lipid and protein composition. 743 17

Cellular activity of cyclic adenosine monophosphate (cAMP)-degrading phosphodiesterases (PDEs) is of crucial importance for the regulation of cAMP levels. However, PDE isoenzymes in human keratinocytes have not been characterized previously. In the present study, the PDE isoenzyme activity profile of the human keratinocyte cell line HaCaT was investigated by PDE activity measurements. In addition, the cAMP-mediated regulation of PDE activities was examined. The isoenzymes PDE IV and PDE V activities were identified in HaCaT cell homogenates by activity measurements and were found to be preferentially located in the soluble fraction. Long-term exposure of HaCaT cells to cAMP-elevating agents (e.g., rolipram, salbutamol, forskolin) triggered a maximum threefold up-regulation of PDE IV activity, whereas PDE V activity was not affected. The PDE IV inhibitor rolipram synergistically amplified PDE IV up-regulation by beta 2-receptor agonists. Experiments applying protein kinase A activators and inhibitors as well as actinomycin D and cycloheximide indicated that de novo mRNA and protein synthesis were at least partly involved in PDE IV up-regulation. Functionally, the enhanced PDE IV activity was reflected by an impaired cAMP response to salbutamol. This hyporesponsiveness toward the beta 2-adrenoceptor agonists was partly reversed by rolipram. This study describes a cAMP-dependent long-term up-regulation of PDE IV in HaCaT cells, which is at least partly reflected by a simultaneous reduced cAMP response to a beta-agonist.
J Invest Dermatol 1995 Jul
PMID:Identification of phosphodiesterase IV activity and its cyclic adenosine monophosphate-dependent up-regulation in a human keratinocyte cell line (HaCaT). 761 79


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