Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in activities of plasma membrane enzymes during liver regeneration may be related to the maintenance of hepatic function or to the regulation of cell proliferation. Plasma membranes were isolated from rat livers at various times after partial hepatectomy, and the specific activities of alkaline phosphatase, (Na+ + K+)-ATPase, leucine aminopeptidase, 5'-nucleotidase, and adenylate cyclase (basal and with glucagon or epinephrine) were measured. Alkaline phosphatase and (Na+ + K+)-ATPase activity increased 3.6-fold and 2-fold respectively, during the first 48 h after partial hepatectomy. The time of onset and duration of change suggest that these increases in activity are involved in the maintenance of bile secretion. Decreases in leucine aminopeptidase activity at 48--108 h and in 5'-nucleotidase activity at 12--24 h were observed, which may be involved in the restoration of protein and accumulation of RNA. The basal activity of adenylate cyclase increased after partial hepatectomy. The response of adenylate cyclase to epinephrine showed a transitory increase between 36 and 108 h after surgery, while the response to glucagon was decreased by approximately 50% at all time points through 324 h after surgery. These changes in the hormone responsiveness of adenylate cyclase are similar to those previously observed in fetal and preneoplastic liver.
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PMID:Changes in plasma membrane enzyme activities during liver regeneration in the rat. 14 24

Two types of plasma membrane were purified from canine distal renal medulla by the techniques of differential and zonal density-gradient centrifugation followed by free-flow electrophoresis. One group of plasma membranes was identified as basal-laterally derived based on a 30-fold enrichment of Na-K-ATPase, a 20-fold enrichment of vasopressin-stimulated adenylate cyclase, and a 33-fold enrichment of [3H]vasopressin binding sites. The second type of plasma membrane was free of these markers, but had a cholesterol and phospholipid composition similar to them. Alkaline phosphatase also had a similar distribution in the two fractions. This lighter membrane fraction contained a membrane-bound cyclic AMP-dependent protein kinase as well as substrate for this kinase. In addition there was a 26-fold enrichment of specific activity of an anion (SO32-)-activated ATPase which was insensitive to mitochondrial ATPase inhibitor protein, in contrast to the mitochondrial fraction of the tissue. Based on the relative preponderance of collecting duct tissue in the distal medulla and the yield of membrane protein, these membranes are tentatively identified as containing apical membranes of the collecting duct.
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PMID:Purification of distinct plasma membranes from canine renal medulla. 20 99

Fractions enriched in hCG-binding activity were prepared by differential rate centrifugation of superovulated rat ovarian homogenates and were applied to continuous sucrose density gradients (20-55%). After centrifugation at 63,000 x gav for 3.5 h, fractions of each gradient were collected and assayed for a range of marker enzyme activities characteristic of surface membranes and subcellular organelles. Mitochondria, lysosomes, and rough and smooth endoplasmic reticulum membranes accumulated in the gradient between 38-41% sucrose (1.165-1.180 g/cm3). Nuclei passed through the gradient. However, the various surface membrane markers concentrated in two distinct regions of the gradient. Alkaline phosphatase, phosphodiesterase, (Na+ + K+)ATPase I, and hCG-binding activity concentrated at 29-32% sucrose (1.120-1.135 g/cm3), whereas 5'-nucleotidase, Mg2+-dependent ATPase, and adenylate cyclase activities (and minor peaks of hCG-binding and phosphodiesterase activities) were enriched at 36-38% sucrose (1.16-1.17 g/cm3). A second ATPase, [(Na+ + K+)ATPase II], was also observed in this region of the gradient, which could be distinguished from (Na+ + K+)ATPase I of the light membrane fraction by its sensitivity to the Ca2+-chelating agent, ethylene glycol bis-(aminoethyl)tetraacetic acid (EGTA). The kinetics of binding of radioiodinated hCG to the gonadotropin receptors of the light and heavy membrane fractions were very similar. It is suggested that fractionation of superovulated rat ovaries yields two distinct populations of surface membrane material which have distinct densities and marker enzyme profiles. Furthermore, in contrast to the heavy membrane fraction, light membranes seem to possess considerable amounts of hCG receptor activity but very little adenylate cyclase.
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PMID:Interactions of gonadotropins with corpus luteum membranes. II. The identification of two distinct surface membrane fractions from superovulated rat ovaries. 21 57

Experimental rats received T-2 toxin (0.063 mg/kg), deoxynivalenol (1.6 mg/kg) and aflatoxin B1 (0.008 mg/kg) during 6 months. Moderately manifest changes were detected in metabolic enzyme activity of foreign substances in the liver and small intestine mucosa. All mycotoxins induced weak hypocalcemia, while ionized calcium concentration in the blood serum decreased only after T-2 toxin administration that was attended by an increase of PTH level. Alkaline phosphatase activity and calcium transport in the small intestine were not significantly changed. Concentration of 25-OHD in the blood serum and 25-hydroxylase D3 activity in the liver decreased in rats given T-2 toxin. Formation of 1,25(OH)2D3 and 24,25(OH)2D3 in the kidneys was not significantly changed, while T-2 toxin inhibited regulatory changes in 1-hydroxylase 25-OHD3 activity in response to the action of PTH and adenylate cyclase activator forskolin. The results of the investigation have evidenced that calcium metabolism disorders during chronic action of mycotoxins could be partially associated with secondary vitamin D deficiency.
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PMID:[Calcium and vitamin D metabolism and enzymes of xenobiotic metabolism during chronic action of mycotoxins]. 227 21

A homogeneous population of single cells from the thick ascending limb of Henle's loop (TALH) has been isolated from the rabbit kidney medulla. A total medullary cell suspension was prepared by a series of collagenase, hyaluronidase, and trypsin digestions and separated on a Ficoll gradient (2.6-30.7% wt/wt). Morphologically, the cells isolated from the TALH were homogeneous and showed polarity within their plasma membrane structure, with a few blunt microvilli on their apical surface and deep infoldings of the basal-lateral membrane. Biochemically, the TALH cells were highly enriched in calcitonin-sensitive adenylate cyclase and Na, K-ATPase. Alkaline phosphatase and arginine vasopressin-sensitive adenylate cyclase, highly concentrated in proximal tubule and collecting duct, were present only in low concentrations in the TALH cells. Additionally, furosemide, a diuretic inhibiting sodium chloride transport in the TALH in vivo, inhibited oxygen consumption of the TALH cells in a dose-dependent manner. The TALH cells were viable, as judged by morphological appearance, trypan blue exclusion, the response of oxygen consumption to 2,4-dinitrophenol, succinate and ouabain, and the cellular Na, K and ATP levels.
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PMID:Separation of renal medullary cells: isolation of cells from the thick ascending limb of Henle's loop. 625 27

Titanium and hydroxyapatite are used for the fabrication of dental and orthopedic implants. The longevity of these implants depends on the amount and rate of bone formation that occurs around their surfaces. In the present study, the effects of titanium, hydroxyapatite, and polystyrene (control) on the proliferation of rat calvarial cells, and on their capacity to express alkaline phosphatase and respond to parathyroid hormone (PTH) stimulation, were studied. The nature of the substrate did not affect the DNA and protein contents of experimental and control cultures throughout the experimental period. Alkaline phosphatase expression and PTH response, as assessed by DNA synthesis and adenylate cyclase activity, were higher in cultures grown on hydroxyapatite and polystyrene than in those grown on titanium. These results indicate that hydroxyapatite was a more favorable substrate than titanium for the growth and differentiation of osteoblast-like cells in vitro.
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PMID:The effects of titanium and hydroxyapatite on osteoblastic expression and proliferation in rat parietal bone cultures. 838 12

Incubation of hepatocytes or the SV40-DNA-immortalized hepatocyte P9 cell line with cholera toxin led to a time-dependent activation of adenylate cyclase activity, which occurred after a defined lag period. When added together with cholera toxin, each of the hormones insulin and vasopressin was capable of attenuating the maximum stimulatory effect achieved by cholera toxin over a period of 60 min through a process which could be blocked by the compounds staurosporine and chelerythrine. Attenuating effects on cholera-toxin-stimulated adenylate cyclase activity could also be elicited by using either the protein kinase C (PKC)-stimulating phorbol ester PMA (phorbol 12-myristate 13-acetate) or the protein phosphatase inhibitor okadaic acid. Alkaline phosphatase treatment of membranes reversed the inhibitory effect of PMA. Cholera toxin also stimulated the adenylate cyclase activity of intact CHO (Chinese-hamster ovary) and NIH-3T3 cells, but this activity was insensitive to the addition of PMA. Overexpression of various PKC isoforms in CHO cell lines did not confer sensitivity to inhibition by PMA upon cholera-toxin-stimulated adenylate cyclase activity. Rather, overexpression of the gamma isoform of PKC allowed PMA to stimulate adenylate cyclase activity in CHO cells. It is suggested that the PKC-mediated phosphorylation of a membrane protein attenuates cholera-toxin-stimulated adenylate cyclase activity in hepatocytes and P9 cells. The cellular selectivity of such an action may be due to the target for this inhibitory action of PKC being a particular isoform of adenylate cyclase which provides the major activity in hepatocytes and P9 cells, but not in either CHO or NIH-3T3 cells.
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PMID:Insulin and vasopressin elicit inhibition of cholera-toxin-stimulated adenylate cyclase activity in both hepatocytes and the P9 immortalized hepatocyte cell line through an action involving protein kinase C. 855 18

The phenotypes of the human renal epithelial cell lines, SK-NEP-1 and G401 (Wilm's tumour lines) and ACHN, A498, A704, Caki-1 and Caki-2 (renal adenocarcinomas), were investigated in order to develop as toxicological model systems, human renal cell lines showing properties similar to those found in discrete renal tubular segments. All cell lines, except G401, demonstrated significant (P < 0.05) stimulation of adenyl cyclase activity by calcitonin. Alkaline phosphatase activity was not detectable in any cell line except for G401. None of the cell lines tested was capable of forming epithelial layers characteristic of 'tight' epithelia. The G401 cell line displayed several characteristics of the proximal nephron including a receptor for hPTH and detectable levels of the brush-border enzymes alkaline phosphatase (0.18 +/- 0.02 mU/mg protein), leucine aminopeptidase (14.0 +/- 5.1 mU/mg protein), glutathione transferase (8.61 +/- 2.53 mU/mg protein) and gamma-glutamyl transpeptidase (24.0 +/- 2.1 mU/mg protein). hPTH (0.01-1 mum) stimulated adenyl cyclase activity in homogenates of G401 cells in a dose-dependent manner, and this stimulation was reversed by 10 mum of the specific PTH antagonist Nle, Tyr-PTH 3-34 amide. The addition of 10 mum antagonist to unstimulated G401 cell homogenate reduced the basal activity of adenyl cyclase from 87.3 +/- 17.4 to 45.9 +/- 13.2 pmol cAMP/mg protein . 15 min. The effect of known nephrotoxic agents was tested on G401 cells by measuring basic mitochondrial enzyme function (MTT assay). The antibiotic gentamicin (5 mm), significantly (P < 0.001) inhibited MTT activity in a dose-dependent manner with a maximum inhibition to23.2 +/- 9.2% of untreated G401 cells. S- (1,1,2,2,tetrafluoroethyl)- l -glutathione (4 mm) and its cysteine conjugate (2.5 mm) reduced MTT activity to 44.0 +/- 10.9% and 33.3 +/- 2.6% of control untreated G401 cells, respectively. We suggest that the G401 cell line may be a useful model of the human proximal tubule in predictive toxicology.
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PMID:Established human renal cell lines: Phenotypic characteristics define suitability for use in in vitro models for predictive toxicology. 2073 80

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