Effect of TRPV1 on Activity of Isoforms of Constitutive Nitric Oxide Synthase during Regulation of Bicarbonate Secretion in the Stomach.

Application of mild irritants (1 M NaCl; pH 2.0) on the gastric mucosa potentiates the protective secretion of bicarbonates by epithelial cells. This response is mainly mediated by capsaicin-sensitive afferent nerve endings located in the submucosa. It was shown that activation of vanilloid type 1 receptors (TRPV1) induced by exogenous acidification of GM is not sufficient to potentiate the production of HCO3, including production depending on neuronal NO synthase. However, the effect of exogenous acid on TRPV1 leads to activation of endothelial NO synthase that restrict the gastric secretion of [Formula: see text].

Interaction of Constitutive Nitric Oxide Synthases with Cyclooxygenases in Regulation of Bicarbonate Secretion in the Gastric Mucosa.

Neuronal NO synthase blocker 7-nitroindazole suppressed bicarbonate secretion in rat gastric mucosa induced by mild local irritation with 1 M NaCl (pH 2.0). Non-selective blocker of neuronal and endothelial synthases, Nω-nitro-L-arginine (L-NNA), did not affect HCO3- production, but inhibited secretion after pretreatment with omeprazole. Non-selective cyclooxygenase blocker indomethacin inhibited HCO3- production under conditions of normal synthase activity and in the presence of L-NNA, but was ineffective when co-administered with 7-nitroindazole. It was concluded that neuronal and endothelial synthases are involved in different mechanisms of regulation of HCO3- secretion in the gastric mucosa induced by mild irritation. Activation of neuronal synthase stimulated HCO3- production, which is mediated mainly through activation of cyclooxygenase. Theoretically, activation of endothelial synthase should suppress HCO3- production. The effect of endothelial synthase depends on acid secretion in the stomach and bicarbonate concentration in the submucosa, as it was demonstrated in experiments with intravenous NaHCO3 infusion.

[Peculiarities of detection of 4-nitro-3-(trifluoromethyl)-aniline in the biological material].

The objective of the present work was to study peculiarities of detection of 4-nitro-3-(trifluoromethyl)-aniline in the biological material with the use of TLC, GC-MS, and electron spectrophotometry. We have proposed the rationale for the application of acetone as an insulating agent for the extraction of 4-nitro-3-(trifluoromethyl)-aniline from the cadaveric hepatic tissue and biological fluids. It was shown that this compound is possible to separate from endogenous biomaterials on the silicagel L column (40/100 mcm). The results of the quantitative evaluation of different amounts of 4-nitro-3-(trifluoromethyl)-aniline in the cadaveric hepatic tissue, blood, plasma, and urine are presented. The proposed method makes it possible to determine a minimum of 0.12 mg of 4-nitro-3-(trifluoromethyl)-aniline in 100 g of the biological material (cadaveric hepatic tissue), 0.09 mg in 100 g of blood, 0.06 mg and 0.05 mg in 100 u of plasma and urine respectively.

[ROLES OF CONSTITUTIVE SYNTHASES OF NITRIC OXIDE IN THE REGULATION OF GASTRIC BICARBONATE SECRETION INDUCED BY MILD IRRITATION OF THE MUCOSA].

Roles of isoforms of constitutive synthase of nitric oxide, neuronal or endothelial (nNOS or eNOS), in control of gastric bicarbonate secretion induced by mild irritation of the gastric mucosa was assessed at the normoacid state or after blockade of gastric acid secretion with omeprazole. In anesthetized rats, the concentration of HCO3- in luminal perfusate was calculated basing on measurements of pH/PCO2. Mucosal irritation during 20 min with acidic hypertonic solution (1 M NaCl, pH 2.0) caused marked and omeprazole-independent increase of HCO-secretion. Selective blocker ofnNOS in vivo 7-nitroindazole (7-NI), and the nonselective blocker ofnNOS and eNOS, N(G)-nitro-L-arginine (L-NNA), were applied either intravenously (10 mg/kg), or locally via retrograde injection into the splenic artery (1 mg/kg). At the normo-acid state, the irritation-induced secretion of was suppressed by 7-NI, but was not affected by L-NNA. After administration of omeprazole, both 7-NI and L-NNA equally inhibited HCO3- output. The effect of 7-NI (but not L-NNA) was abolished by cyclooxygenase (COX) inhibitor, indomethacin, which by itself suppressed irritation-induced secretion of HCO3-. Additionally, bicarbonate output was substantially reduced by the blocker of soluble guanylate cyclase (GC), methylene blue. We conclude that irritation-induced secretion of HCO3- is largely mediated by intramural nNOS and depends on GC-COX interaction. As it was theoretically estimated, eNOS activity caused a reduction of HCO3- output in the normo-acid stomach. Omeprazole abolished the effect of eNOS.

Lactoferrin from canine neutrophils: isolation and physicochemical and antimicrobial properties.

Lactoferrin has been isolated from canine leukocytes for the first time. Lactoferrin was identified by N-terminal amino acid sequence and by capability to capture ferric cations resulting in a complex with absorbance maximum at 460-470 nm. It is demonstrated that canine lactoferrin resembles the human homolog in some physicochemical properties, i.e. molecular weight, carbohydrate presence, and conditions of protein-iron complex dissociation. Bactericidal activity of dog lactoferrin was demonstrated on the gram-negative bacterium Escherichia coli and gram-positive bacterium Listeria monocytogenes. Bactericidal activity of canine lactoferrin is similar to that of human lactoferrin.