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L L Norling

Publications and source records attributed to L L Norling.

24 records · Page 2Linked to original sources
PubMed1985

Comparison of Ca2+ -dependent phosphorylation in viable dispersed brain cells with calmodulin-dependent protein kinase activity in cell-free preparations of rat brain.

Using two depolarizing agents, veratrine and high concentrations of extracellular KCl, we studied depolarization-stimulated phosphorylations in 32P-labelled dispersed brain tissue in order to identify phosphoprotein substrates for Ca2+ - and calmodulin-dependent protein kinase activity at the cellular level, for comparison with findings in cell-free preparations. In intact brain cells, the only prominent depolarization-stimulated phosphorylation was a 77 kDa protein separated on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. This phosphorylation was dependent on external Ca2+, since chelation of Ca2+ in media with 6 mM-EGTA or the presence of verapamil (a Ca2+ -channel blocker) in the incubation media inhibited depolarization-stimulated phosphorylation of the 77 kDa protein. Phosphorylation of the 77 kDa protein also appeared to be dependent on calmodulin, because depolarization-stimulated phosphorylation was significantly decreased (P less than 0.05) when 100 microM-trifluoperazine was present in the incubation media. Polymyxin B, an inhibitor of Ca2+- and phospholipid-dependent phosphorylation, and 12-O-tetradecanoylphorbol 13-acetate, the phorbol ester enhancing Ca2+- and phospholipid-dependent phosphorylation, had no effect on the phosphorylation of the 77 kDa protein. The 77 kDa phosphoprotein was identified as a protein previously named synapsin I [Ueda, Maeno & Greengard (1973) J. Biol. Chem 248, 8295-8305] on the basis of similar migration of native and proteolytic fragments of the 77 kDa protein with those of authentic synapsin I on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Whereas several studies with cell-free preparations showed that 57 kDa and 54 kDa endogenous phosphoproteins were the most prominent species phosphorylated in a Ca2+ and calmodulin-dependent manner, these results indicate that synapsin is the most prominent Ca2+-and calmodulin-dependent phosphorylation in intact cells. The phosphorylations of 54 kDa and 57 kDa proteins may not be as important in vivo, but instead occur as a result of the disruption of cellular integrity inherent in preparation of cell-free subfractions of brain tissue.

Animals↗
PubMed1984

Specificity of inhibition of calcium- and calmodulin-dependent protein kinase by alloxan.

Studies were undertaken to determine whether the effect of alloxan to inactivate a membrane-bound calcium- and calmodulin-dependent protein kinase was specific for the pancreatic islets and whether inactivation of the kinase occurred also after injection of a diabetogenic dose of alloxan into rats. The effect of alloxan was also examined on similar particulate calcium- and calmodulin-dependent kinases present in two other secretory tissues, mammary acini and forebrain. Exposure of alloxan to cell-free preparations of all secretory tissues examined inhibited the calcium- and calmodulin-dependent kinase activities, suggesting that the specificity of alloxan action was not due to the presence in islets of a kinase uniquely sensitive to alloxan. To determine whether the selective effect of alloxan action was mediated at the cellular level, experiments were performed with alloxan presented to intact cells. Whereas alloxan exposure to viable cell preparations of islets and brain decreased the subsequently measured calcium- and calmodulin-dependent protein kinase activity, the activity measured in mammary acini exposed to these alloxan concentrations was unaffected. Injection (i.v.) of a diabetogenic dose of alloxan (50 mg/kg) produced an immediate (10 min) and selective inactivation of the calcium- and calmodulin-dependent protein kinase in pancreatic islets but had no effect on the similar kinases measured in brain and mammary acini. These results indicate that the unique sensitivity of islets to alloxan may result from the ability of alloxan to rapidly gain intracellular access and then inactivate this kinase activity. The selective effect of alloxan injection on this islet protein kinase is consistent with the hypothesis that inactivation of the kinase by alloxan is related to its diabetogenic effect in vivo.

Alloxan↗
PubMed1978

Nucleoside 5'-monophosphate analogues. Synthesis of 5'-sulfamino-5'-deoxynucleosides.

The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be quite stable to hydrolysis in acidic or basic aqueous solution Tests show that these compounds do not inhibit the growth of Escherichia coli or L1210 cells at concentrations less than 10(-4) M. At 10(-4) M compound 2 was found to give 70% inhibition of the replication of herpes simplex virus (type 1) with no effect on host cell growth (CV-1 monkey line).

Adenosine↗
PubMedDate not supplied

Prenatal maternal indomethacin use resulting in prolonged neonatal renal insufficiency.

The short-term use of indomethacin has been shown to be relatively safe and effective in halting premature labor. Its use has been associated with adverse renal effects in both the fetal and newborn periods that are generally transient and resolve on discontinuation of the drug. However, limited data suggest that prolonged prenatal exposure to indomethacin may be harmful to the fetus. We report a case of prolonged severe renal dysfunction characterized by oligohydramnios and postnatal anuria, azotemia, and ultrasonographic kidney abnormalities associated with the long-term prenatal use of indomethacin. Although partial resolution was observed, a moderate decrease in renal function persists. Prenatal maternal indomethacin use represents a potential cause of renal dysfunction in the newborn infant that may be only partially reversible.

Adult↗