Local anesthetics: A new class of partial inhibitors of mitochondrial ATPase

The following characteristics are reported for mitochondrial ATPase prepared by the chloroform extraction method: (1) The pH optimum for enzyme activity is at 8.0. (2) The neutral anesthetic benzocaine inhibits the enzyme at all pH values. (3) Reciprocal plots of 1/v versus 1/[ATP] show that inhibition by lidocaine, tetracaine, dibucaine, and chlorpromazine is noncompetitive; slope and intercept replots are hyperbolic, showing that the inhibition is partial rather than complete.     

Steroid antagonism of the ‘hypertensinogenic’ activity of 9α-fluoroprednisolone

We have previously reported that adrenocortical steroids raise blood pressure by a ‘hypertensinogenic’ mechanism of action which is not simply related to their classical ‘mineralocorticoid’ or ‘glucocorticoid’ actions. This study presents evidence for specific antagonism of this ‘hypertensinogenic’ activity. The effects of separate IV infusions of prednisolone (P) 100 mg/d and 9α-fluoro-prednisolone (9αF-P) 0.6 mg/d on mean arterial pressure (MAP), plasma [K], plasma [glucose] and urinary NA excretion (UNaV) after 2 days were studied in sheep. In the same group of sheep which received P alone for 2 days, 9αF-P was given for a further 2 days while continuing the P infusion (P + 9αF-P). P alone had no effect on MAP or plasma [K] or U_NaV but increased plasma [glucose], effects which are characteristic of ‘glucocorticoid’ activity. 9αF-P alone increased MAP by 14 mmHg (P<0.001) and reduced plasma [K] and U_NaV but had no effect on plasma [glucose]. Thus 9αF-P exhibited both ‘hypertensinogenic’ and ‘mineralocorticoid’ activity. In the sheep which received the combined P + 9αF-P infusion, the increase in MAP normally produced by 9αF-P was blocked. Although pretreatment with P blocked the pressor effect of 9αF-P, it did not alter the ‘mineralocorticoid’ effects, namely hypokalaemia and urinary Na retention, produced when 9αF-P was infused alone. These results provide further evidence for our concept of a ‘hypertensinogenic’ class of steroid activity and are the first demonstration of specific antagonism of steroid induced hypertension.     

Selectivity of lipid-protein interactions

The spin label ESR and intrinsic fluorescence quenching methods of determining the selectivity of interactions of lipids with integral membrane proteins are summarized. The selectivity patterns of phospholipids, fatty acids, and steroids are reviewed for a variety of integral proteins. Where appropriate, correlations are established with biochemical assays of the effects of specific lipids on enzymatic activity and transport function.     

The evolution of migration and some life history parameters in marine fishes

Synopsis Migration is a common phenomenon in marine fishes but the consequences with respect to life history variation have been little explored. Migration both influences the evolution of other traits and is contigent upon the evolution of other behavioural and demographic characters. The interaction between such factors is illustrated by considering the relationship between the cost of migration in relation to fecundity and the advantages and disadvantages of schooling, a phenomenon hypothesized to favour the evolution of migration. These analyses predict that migratory species will be relatively large, mature late and at a relatively large size and grow relatively fast. Data from north temperate marine fish support these predictions.     

[3H]Arachidonic acid metabolism in rat brain minces: Effects of nucleotide triphosphates,CDPcholine and CMP

Rat brain minces were used to investigate the effects of nucleotides on the metabolism of arachidonic acid in nerve tissue. Brain free fatty acids, neutral lipids and phospholipids, were radiolabeled in vivo following intracerebral injection of [³H]arachidonic acid. Minces were prepared from the radiolabeled cerebra and were incubated in a modified Krebs-Ringer buffer with and without various nucleotides. The incubation-induced accumulation of unesterified [³H]arachidonate was reduced in the presence of CDPcholine, ATP, CTP, GTP, and UTP. These nucleotides inhibited choline and inositol glycerophospholipid hydrolysis. They also reduced the amount of labeled diglycerides. However, CDPethanolamine had no effect on arachidonic acid metabolism in the mince preparation and CMP appeared to stimulate further hydrolysis of choline glycerophospholipids, resulting in increased accumulation of [³H]arachidonic acid and labeled diglycerides. We suggest that the production of unesterified [³H]arachidonate and labeled diglycerides is due to the involvement of more than one catabolic reaction, since the high energy nucleotides had similar effects on fatty acid accumulation, but different effects on phospholipid labeling.     

Insulin receptors in the brain: Structural and physiological characterization

The present study was conducted to characterize insulin receptors and to determine the effects of insulin in synaptosomes prepared from adult rat brains. Binding of¹²⁵I-insulin to synaptosome insulin receptors was highly specific and time dependent: equilibrium binding was obtained within 60 minutes, and a t_1/2 of dissociation of 26 minutes. Cross-linking of¹²⁵I-insulin to its receptor followed by SDS-PAGE demonstrated that the apparent molecular weight of the alpha subunit of the receptor was 122,000 compared with 134,000 for the liver insulin receptor. In addition, insulin stimulated the dose-dependent phosphorylation of exogenous tyrosine containing substrate and a 95,000 MW plasma membrane associated protein, in a lectin-purified insulin receptor preparation. The membrane associated protein was determined to be the subunit of the insulin receptor. Incubation of synaptosomes with insulin caused a dose-dependent inhibition of specific sodium-sensitive [³H]norepinephrine uptake. Insulin inhibition of [³H]norepinephrine uptake was mediated by a decrease in active uptake sites without any effects in theK _m, and was specific for insulin since related and unrelated peptides influenced the uptake in proportion to their structural similarity with insulin. These observations indicate that synaptosomes prepared from the adult rat brain possess specific insulin receptors and insulin has inhibitory effects on norepinephrine uptake in the preparation.     

Competitive Mechanisms for Inhibition of Sulfate Reduction and Methane Production in the Zone of Ferric Iron Reduction in Sediments

Mechanisms for inhibition of sulfate reduction and methane production in the zone of Fe(III) reduction in sediments were investigated. Addition of amorphic iron(III) oxyhydroxide to sediments in which sulfate reduction was the predominant terminal electron-accepting process inhibited sulfate reduction 86 to 100%. The decrease in electron flow to sulfate reduction was accompanied by a corresponding increase in electron flow to Fe(III) reduction. In a similar manner, Fe(III) additions also inhibited methane production in sulfate-depleted sediments. The inhibition of sulfate reduction and methane production was the result of substrate limitation, because the sediments retained the potential for sulfate reduction and methane production in the presence of excess hydrogen and acetate. Sediments in which Fe(III) reduction was the predominant terminal electron-accepting process had much lower concentrations of hydrogen and acetate than sediments in which sulfate reduction or methane production was the predominant terminal process. The low concentrations of hydrogen and acetate in the Fe(III)-reducing sediments were the result of metabolism by Fe(III)-reducing organisms of hydrogen and acetate at concentrations lower than sulfate reducers or methanogens could metabolize them. The results indicate that when Fe(III) is in a form that Fe(III)-reducing organisms can readily reduce, Fe(III)-reducing organisms can inhibit sulfate reduction and methane production by outcompeting sulfate reducers and methanogens for electron donors.     

Cytochrome distribution across chloroplast thylakoid membranes. Controlled proteolysis of inside-out and right-side-out vesicles

The transverse distribution of chloroplast cytochromes b-559 (high and low potentials), b-563 and f in pea thylakoid membranes was studied by the effects of trypsin and pronase on inside-out and right-side-out thylakoid vesicles. The high potential (HP) form of cytochrome b-559 was degraded to a low potential (LP) form most rapidly in right-side-out vesicles. In either type of vesicle there was no overall loss of the cytochrome from the membrane. This suggests that the haem group is buried in the membrane but that the cytochrome environment is most labile at the outer surface. Cytochrome b-563 was unaffected by trypsin and only slightly degraded by pronase in inverted vesicles. However, pronase caused the loss of an M_r 1000, non-haem fraction from the cytochrome f polypeptide in inside-out vesices only. The total cytochrome f content (measured spectrophotometrically and by staining polyacrylamide gels for haem associated peroxidase activity) decayed only slightly in either type of vesicle. These observations suggest that cytochrome f is, in part, exposed to the intrathylakoid lumen, whilst its haem group is retained in a more hydrophobic region.     

The phenology and economic potential of Terminalia catappa L. in South-Central Ghana

Terminalia catappa L. (popularly known as Indian almond in Ghana) is a distinctive tree much used in West Africa for shade and as an ornamental plant. By careful observation of the species generally in south-central Ghana, and by a detailed day-by-day analysis for one year of the leaf, fruit and litter production of one typical mature tree, and by chemical analysis of its leaves and fruit, so the phenology and possible economic potential of the species were assessed. In the region of study the main elements in the phenology are two main flushing periods immediately following two main periods of leaf shedding, which occur at the equinoxes, and two major fruit-fall periods which precede the leaf shedding by one month. Fruiting takes place in four main spells, however, and flowering in three. Any or all of the processes may overlap in time. The tree is little used economically, but it is suggested that it might have value not only for shade and ornament but also as a food source and a provider of firewood, building timber, mulch and fertiliser, cooking oil, gum and tannin. Experimental commercial planting of the tree is proposed.     

Increased Intracellular Cyclic AMP Differentially Modulates Nerve Growth Factor Induction of Three Neuronal Recognition Molecules Involved in Neurite Outgrowth

The relative expression of the immunoglobulin superfamily members Thy-1 and L1 and the neural cell adhesion molecule (N-CAM) in PC12 cells grown in the presence of nerve growth factor (NGF), cholera toxin, or both has been quantified. Whereas NGF treatment induced increases in the cell surface expression of all three glycoproteins, treatment with cholera toxin resulted in the specific induction of L1. During the first few days of culture, cholera toxin acted synergistically with NGF to promote increases in neuritic outgrowth and the synthesis and cell surface accumulation of the 140- and 180-kilodalton subunits of N-CAM. In contrast, over the same period of culture, cholera toxin inhibited the NGF induction of Thy-1 and L1. Over longer periods of culture (3-5 days), cholera toxin inhibited the NGF induction of N-CAM and neurite outgrowth. A similar pattern of synergistic and inhibitory responses was observed when differentiation was induced by fibroblast growth factor (FGF) rather than NGF or when cholera toxin was replaced with forskolin. These data suggest that intracellular cyclic AMP can differentially modulate cell surface glycoprotein expression induced by either NGF or FGF. Of the three cell surface glycoproteins we have studied, temporal changes in N-CAM expression correlate best with the morphological differentiation status of PC12 cells.