Send rep#{241}nt requests to: A Major Plasma Metabolite of Chlorpromazine in a Population of Chronic Schizophrenics

ABSTRACT: (Received July 29, 1985; accepted November 3, 1985) N-Demethylatio

3,5-Di-t-butylcatechol as a ryanodine receptor agonist in rat intact skeletal muscle fibers

3,5-Di-t-butylcatechol (DTCAT) stimulates the rat skeletal muscle sarcoplasmic reticulum ryanodine receptor (RyR). In the present study, its effects on the contractile response of diaphragm preparation were characterized using electrically stimulated phrenic nerve–diaphragm preparations and diaphragm strips. DTCAT reduced, concentration-dependently, twitch contraction of the phrenic nerve– diaphragm preparation evoked by both direct and indirect stimulation and increased spontaneous tone. Twitch amplitude reduction was irreversible, while the increase of spontaneous tone was only partially reversible upon DTCAT washout. In diaphragm strips, caffeine > 4-chloro-m-cresol >> 3,5-diisopropylcatechol = ryanodine > DTCAT enhanced spontaneous tone, whereas quercetin reduced it with all the compounds reducing twitch amplitude. DTCAT-induced contracture was partly dependent on extracellular Ca2+ influx and antagonized by a Cd2+/La3+ mixture. In intact skeletal muscle preparations, DTCAT behaved as a RyR agonist

Vasoactive intestinal peptide protects guinea-pig detrusor nerves from anoxia/glucopenia injury

Vasoactive intestinal peptide (VIP) was tested for its capability to protect the intrinsic nerves of guinea-pig urinary bladder from damage due to anoxia/glucopenia and reperfusion. Guinea-pig detrusor strips were mounted for tension recording in small organ baths and the nerves were subjected to electric field stimulation. VIP (0.3 microM) improved significantly the response of strips to electrical field stimulation either during anoxia/glucopenia or thereafter during reperfusion, as compared to untreated tissues. The antioxidant activity of VIP assessed as its capability to scavenge peroxyl radicals during linoleic acid oxidation corresponded to 6.42+/-0.13 pIC(50) M, i.e. close to the concentration proved to protect strips against the anoxic--glucopenic and reperfusion damage

Interaction of butylated hydroxyanisole with mitochondrial oxidative phosphorylation

The antioxidant, butylated hydroxyanisole (BHA), has a number of effects on mitochondrial oxidative phosphorylation. In this study we apply the novel approach developed by Brand (Brand MD, Biochim Biophys Acta 1018: 128-133, 1990) to investigate the site of action of BHA on oxidative phosphorylation in rat liver mitochondria. Using this approach we show that BHA increases the proton leak through the mitochondrial inner membrane and that it also inhibits the delta p (proton motive force across the mitochondrial inner membrane) generating system, but has no effect on the phosphorylation system. This demonstrates that compounds having pleiotypic effects on mitochondrial oxidative phosphorylation in vitro can be analysed and their many effects distinguished. This approach is of general use in analysing many other compounds of pharmacological interest which interact with mitochondria. The implications of these results for the mechanism of interaction of BHA with mitochondrial oxidative phosphorylation are discussed

Purification and characterization of rat intestinal peroxidase. Its activity towards 2-t-butyl-4-methoxyphenol (BHA).

Impure preparations of rat intestinal peroxidase were shown to aggregate at low ionic strengths and to disaggregate at higher values. This aggregation was accompanied by a decrease in specific activity, which could lead to hysteretic behaviour of reaction progress curves. Advantage was taken of this reversible aggregation to obtain a relatively pure extract, which was subsequently purified to apparent homogeneity by affinity chromatography on concanavalin A-Sepharose followed by hydrophobic chromatography. The purified enzyme did not show the ionic-strength-dependent aggregation behaviour, behaving as a monomer of Mr 50,000. The purified enzyme was shown to catalyse the peroxidatic conversion of the commonly used antioxidant 2-t-butyl-4-methoxyphenol (butylated hydroxyanisole, BHA) to form 3,3'-di-t-butyl-2,2'-dihydroxy-5,5'-dimethoxybiphenyl, with a Km value of 176 microM and a maximum velocity of 8 mumol/min per mg. The specificity constant, kcat./Km, for this substrate was similar to that shown towards the substrate guaiacol

Freeze-dried red wine effects on cardiac function and ECG of the Langendorff-perfused rat heart

The effect of freeze-dried red wine (FDRW) on cardiac function and electrocardiogram (ECG) in Langendorff-isolated rat hearts was investigated. FDRW significantly decreased left ventricular pressure and coronary perfusion pressure, the latter being dependent on the activation of both phosphatidylinositol 3-kinase and eNOS. FDRW did not affect the QRS and QT interval in the ECG, although at 56 μg of gallic acid equivalents/mL, it prolonged PQ interval and induced a second-degree atrioventricular block in 3 out of 6 hearts. This is the first study demonstrating that at concentrations resembling a moderate consumption of red wine, FDRW exhibited negative inotropic and coronary vasodilating activity leaving unaltered ECG, whereas at very high concentrations, it induced arrhythmogenic effects