Synaptosomal membrane activity

Edelfors S, Raven-Jonsen A. 1992. Effect of organic solvents on nervous cell membrane as measured by changes in the calcium magnesium ATPase activity and fluidity of synaptosomal membrane. Pharmacology and Toxicology 70(3) 181-187. 

Anandamide inhibited the specific binding of [ H]-HU-243 to synaptosomal membranes in a manner typical of competitive ligands, with an inhibition constant (K ) of 39.0 + 5.0 nM. In this system, the of tsP-THC, a psychoactive compound of cannabis, was 46.0 + 3-0 nM. These were exciting results — the psychoactive compound from a higher plant and a chemically completely different compound in the brain were found to bind to the same brain receptor at about the same level of activity. Soon after the identification of anandamide, this compound was tested for its pharmacological activity. Anandamide administered i.p. in mice, caused... 

Subcellular membrane-bound enzymes activity. Oil, administered to male CFY weanling rats at a dose of 20% for 16 weeks, produced an increase of synaptosomal acetylcholinesterase activity in the coconut oil-fed group. The Mg -adenosine triphosphate (ATPase) activity was similar among all groups in all the brain regions Superoxide production inhibition. Seed oil, administered to rats at a concentration of 8% of diet, produced equivocal effect on macrophages. Capsaicin or curcumin enhanced effect . ... 

Parameter Nerve ending fraction Activity (or concentration) total specific Synaptosomal membrane fraction Activity (or concentration) total specific Enrichment ... 

Figure 6. Effect of CMP-NeuAc concentration (V/S), of pH (V/pH), of enzymatic protein concentration (V/protein), and of incubation time (V/t) on the activity of synaptosomal membrane-bound sialyltransferase. Calf brain cortex. Acceptor substrates for sialyltransf erase (if) lactosylceramide ( ) desialylated fetuin (%) endogenous glycoprotein (endogenous glycolipids.

Gotow T, Miyaguchi K, Hashimoto PH (1991) Cytoplasmic architecture of the axon terminal filamentous strands specifically associated with synaptic vesicles. Neuroscience 40 587-98 Gower H, Rodnight R, Brammer MJ (1986) Ca2+ sensitivity of Ca2+-dependent protein kinase activities toward intrinsic proteins in synaptosomal membrane fragments from rat cerebral tissue. J Neurochem 46 440-7... 

Changes in EFA status affect the activity of several membrane-associated enzymes and proteins 68-71 Reduced adenyl cyclase activity occurred in EFA-deficient animals,72 while in animals supplemented with n-6 or n-3 fatty acids, increased adenyl cyclase activity was seen in cardiac membranes.73,74 However, the opposite effect has been reported in other membranes, possibly reflecting differences in initial fatty acid composition.75 n-3 PUFAs have been shown to activate membrane Ca-ATPase and inhibit Na, K-ATPase in isolated basolateral membranes from rat duodenal enterocytes76 and inhibit both Ca-ATPase and Na,K-ATPase activity in synaptosomal membranes isolated from rat cerebral cortex.77 EFAs have the ability to modify neuronal Ca-ATPase activity... 

Ap-mediated activation of calcineurin, resulting in dephosphorylation and activation of STEP [191], and (2) Ap-inhibition of the protea-some, resulting in decreased degradation of STEP [197]. As a result, STEP activity is increased in AD, leading to loss of NMDA and AMPA receptors from synaptosomal membranes. Collectively, these studies suggest that inhibition of STEP activity may be beneficial in AD treatment, and validate STEP as a novel drug target in AD (and perhaps other neuropsychiatric disorders, reviewed in ref 131). 

Sellaijevic, L., Kriolica, K., and Boskovic, B., The effect of soman poisoning on phos-phorylating capability and adenylate cyclase activity of isolated synaptosomal membranes. Biochem. Pharmacol, 33, 3714, 1984. 

Yessotoxin inhibited purihed protein phosphatase 2A with an EC50 of 0.36 mg/mL. This activity is lower than that of the classical protein phosphatase inhibitors (okadaic acid, dinophy-sistoxins) by four orders of magnitude [55], Unlike brevetoxins and ciguatoxins, yessotoxin and di-desulfoyessotoxin do not bind to the voltage-gated sodium channel of synaptosomal membranes from rat brain [62],... 

Scheer, H., and Meldolesi, J. (1985). Purification of the Putative a-latrotoxin Receptor from Bovine Synaptosomal Membranes in an Active Binding Form, EMBO J. 4 323 327. This protocol is incomplete (Scheer incubates the wells for 2 h at 4° C) with radioactive a-latrotoxin. He also fails to tell how the radioactivity gets out of the wells, but with 150 [tl 0.1 M NaOH this should be no problem. 

Preti, A., Fiorilli, A., Lombardo, A., Caimi, L., and Tettamanti, G., 1980, Occurrence of sialyl-transferase activity in the synaptosomal membranes prepared from calf brain cortex, J. Biol. Chem., 255 281-296. 

The membrane-bound lysosomal enzyme in rat brain has been solubilized from the particulate fraction and partially purified (Miyagi et aL, 1990a). The sialidase activity can be separated into two peaks, corresponding to sialidases I and II, by AH-Sepharose column chromatography. Using specific antibodies against the enzymes, it has been shown that sialidase I is localized in synaptosomal membranes, and sialidase II in both synaptosomal and lysosomal membranes. The latter species has been further purified by 2150-fold with a recovery of 0.7%. 

Recent studies have suggested that certain plasma membrane-bound siali-dases are linked to the membranes via a GPI anchor, as observed with the sialidase from T. cruzi (Rosenberg et al., 1991). Phosphatidylinositol-specific phospholipase C (PIPLC) released sialidase activity (28% of total) from purified synaptosomal membranes of pig brain, but not from lysosomal membranes (Chiarini et al., 1990). The presence of GPI-anchored sialidase was also shown in human erythrocyte membranes (Chiarini et al., 1993). On the other hand, the sialidase activity in rat brain myelin could not be solubilized with PIPLC despite a concomitant release of alkaline phosphatase activity (about 40% of total), suggesting a different mode of association of the enzyme with the membranes (Saito and Yu, unpublished data). 

Zylinska, L., Gromadzinska, E., and Lachowicz, L. (1996) Okadaic acid as a probe for regulation in vitro of Mg, Ca -ATPase activity in rat cortical and cerebellar synaptosomal membranes. Cell, Signal, 8, 443-448. 

ATP certainly fulfils the criteria for a NT. It is mostly synthesised by mitochondrial oxidative phosphorylation using glucose taken up by the nerve terminal. Much of that ATP is, of course, required to help maintain Na+/K+ ATPase activity and the resting membrane potential as well as a Ca +ATPase, protein kinases and the vesicular binding and release of various NTs. But that leaves some for release as a NT. This has been shown in many peripheral tissues and organs with sympathetic and parasympathetic innervation as well as in brain slices, synaptosomes and from in vivo studies with microdialysis and the cortical cup. There is also evidence that in sympathetically innervated tissue some extracellular ATP originates from the activated postsynaptic cell. While most of the released ATP comes from vesicles containing other NTs, some... 

Mehorta and coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered 0.5-10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of calmodulin, indicating disruption of membrane Ca+2 transport mechanisms exogenous addition of calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater inhibition in brain preparations (Mehorta et al. 1989). However, endrin showed no inhibitory effects on the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes (Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the activities of adenylate cyclase or 3, 5 -cyclic phosphodiesterase, two enzymes associated with synaptic cyclic AMP metabolism (Kodavanti et al. 1988). 

At the cellular level, chlordecone causes spontaneous neurotransmitter release (End et al. 1981) and increases in free intracellular calcium in synaptosomes (Bondy and Halsall 1988 Bondy and McKee 1990 Bondy et al. 1989 Komulainen and Bondy 1987). This appears to be due at least in part to increased permeability of the plasma membrane (Bondy and Halsall 1988 Bondy and McKee 1990 Bondy et al. 1989 Komulainen and Bondy 1987), activation of voltage-dependent calcium channels (Komulainen and Bondy 1987), and inhibition of brain mitochondrial calcium uptake (End et al. 1979, 1981). 

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