Diethyl ether elicited a dose-dependent increase in the intrinsic frequency of contraction of isolated rat atrial preparations. The maximum effect (plus 34 per cent) occurred with 230 mg ether/100 ml medium. This ether concentration corresponds to a partial pressure of 29.2 mm Hg or 3 MAC. The positive chronotropic action of ether was not reduced in atria obtained from rats pretreated with reserpine (4 mg/kg, ip) although this treatment markedly reduced the effect of tyramine on frequency of contraction. The positive chronotropic response to 0.01 muM isoproterenol was inhibited by the beta-adrenergic antagonist 0.3 mgM dl-propranolol but remained unimpaired in the presence of 0.3 mgM d-propranolol (a much weaker antagonist). In contrast, the atrial response to ether was similar in the presence of either d- or dl-propranolol. Atropine, in concentrations that completely blocked the negative chronotropic action of acetylcholine, did not increase the frequency of contraction, suggesting that the positive chronotropic effect of ether is not due to an atropine-like activity of ether. Our results indicate that the positive chronotropic effect of ether on isolated rat atrial preparations is not mediated via catecholamine release, nor does it represent direct stimulation of beta-adrenergic receptors or block of cholinergic receptors. (Key words: Anesthetics, volatile, diethyl ether; Heart, atria, diethyl ether.).

Adrenergic beta-Antagonists↗

PubMed1975

Histochemical localization of glutathione in tissues.

A histochemical method has been developed for the localization of glutathione (GSH) in frozen sections from various tissues including liver, lung, kidney, testis and eye. The reliability and specificity of the method has been investigated by comparing the rates of reaction in tissue and gelatin sections and after depletion of GSH in liver by diethyl maleate. In principle, the method is based on the formation of an irreversible complex of mercury orange with the --SH group of GSH. A 5-min staining period was found to be optimal for staining the --SH group of GSH. In brief, frozen sections 8 mu thick are stained with a 50 muM solution of mercury orange dissolved in toluene, counterstained in 0.05 per cent methylene blue and mounted in Histoclad. Pretreatment of the sections with fixatives or drying them in air completely prevented the staining. In hepatic lobules the brick red granules of the GSH mercury orange complex were distributed uniformly, whereas in other tissues they were not uniform. The GSH staining was localized in the proximal convoluted tubules in the cortex of the kidney, the interalveolar epithelial cells of lungs, the epididymis and the capsule of testis, epithelial cells of vas deferens and the periphery of the lens.

Animals↗

PubMed1975

Metabolism, tissue distribution and covalent binding of tripelennamine and its N-nitroso derivative in the rat.

Benzyl-14C-labeled tripelennamine and its N-nitroso derivative (NDT) were administered (20 mg/kg; 50 muc/kg i.p.) separately to control and phenobarbital-pretreated rats. Tissue distribution and covalent binding of the two compounds in liver, lung, kidney, fat and muscle tissues, as well as in the plasma, were determined at 4 and 24 hours after the administration. No specific localization of the test compounds to any tissue or to the plasma was observed. The in vivo covalent binding of both the compounds to the proteins of the tissues and plasma was low; the highest binding occurred in the liver (approximately 25 pmol/mg of protein). Within 24 hours about 78% of the injected tripelennamine and its metabolites was excreted into the urine whereas only about 35% of the radioactivity of NDT was eliminated. Pretreatment with phenobarbital accelerated the elimination of both substances. The metabolites of the drug and NDT were isolated from urine, hydrolyzed by glucuronidase-sulfatase and identified as their trimethylsilyl derivatives by gas chromatography-mass spectrometry. Tripelennamine was found to be extensively metabolized by N-demethylation and aromatic hydroxylation pathways. By contrast most of the NDT was eliminated as NDT and hydroxylated metabolites; very little was excreted as N-demethylated metabolites. The hydroxylated metabolites identified were p-hydroxybenzyl, p-hydroxybenzyl-5-hydroxypyridyl and m,p-dihydroxybenzyl derivatives of the drug, its N-demethylated analog and NDT. The catechol formation with NDT was found to be 4 times that observed with tripelennamine.

Animals↗

PubMed1975

Blood and urine concentration of chrome in chrome industry workers.

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Chemical Industry↗

PubMed1975

A rapid method for the assay of guanylate cyclase.

An extremely rapid and sensitive assay for guanylate cyclase utilizing [alpha-32P]-GTP has been developed. It involves incubation of 5-100 mug of enzyme protein with 1 mM [alpha-32P]-GTP in 40 mM Tris HC1 buffer (pH 7.4) containing 3-3 mM MnSO2, 10 mM theophylline and 1 mM cyclic GMP. The reaction is terminated by addition of EDTA, and [32P]-cyclic GMP formed is isolated by sequential chromatography on Dowex-50-H+ and alumina. Recovery of 75-85% of [3H]-cyclic GMP and a blank of 0.001-0.003% of added [32P]-GTP was routinely obtained. The [32P] radioactivity isolated was shown to be cyclic GMP by a variety of techniques. The assay has also been shown to be applicable for a variety of tissues.

Adrenal Glands↗

PubMed1975