Angiotensin II inhibits the uptake and removal of [3H]metaraminol by rat lung in vitro.
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Biomedical subjects
Publications and source records attributed to D Davila.
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Uptake of 14C-labelled 5-hydroxytryptamine (14C-5-HT) has been investigated by perfusion of the rat brain ventricular system. When angiotensin II was present during perfusion, a dose-dependent inhibition of 14C-5-HT uptake in rat brain was observed. A similar effect was obtained with angiotensin II analogs (8-alanine angiotensin II or 1-dimethylglycine, 8-isoleucine angiotensin II). The inhibitory effect of angiotensin II can be almost completely blocked with 1-dimethylglycine, 8-isoleucine angiotensin II. In washout experiments, the radioactivity remaining in the brain was greater in the presence of angiotensin II.
The accumulation of 3H-metaraminol in incubated lung tissue of the rat was examined in vitro. Lung tissue concentrated tritium after incubation with 3H-metaraminol. This uptake proceeds against a concentration gradient and shows saturation kinetics (Km 12.5 X 10(-7) M and Vmax 2.105 nM/g/15 min.) with great affinity for 3H-metaraminol. The accumulation of 3H-metaraminol is dependent of temperature and energy supply, and requires the presence of sodium ions. The loss of accumulated radioactivity showed the possibility that a small fraction of metaraminol is apparently firmly boune (e.g. neuronal sites), while a greater portion is taken up by extraneuronal structures (e.g. capillary endothelial cells). The first localization could represent uptake-1 and the second uptake-2. The results obtained also confirm the important role of the lungs as an organ which participates in the fate of endogenous substances and drugs.
Uptake and release of 3H-metaraminol was measured in vitro incubating rat lung tissue in the presence of ouabain (1.5-45 mug/ml), cocaine (1-30 mug/ml), tyramine (0.1-3 mug/ml, reserpine (0.05-1.5 mug/ml), imipramine (0.1-3 mug/ml) and desipramine (0.3-10 mug/ml. All drugs significantly inhibited uptake and release of 3H-metaraminol from lung tissue. This blockade most probably occurs at membrane levels of both neuronal uptake-1 sites and extraneuronal uptake-2 sites. These results further emphasize the importance of the lung in the fate of drugs and endogenous substances.
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With a view to creating national tables of the delayed hypersensitivity response, a total of 1476 healthy persons were studied at eight different locations in Spain. For the measurement of delayed cellular immunity response, Multitest IMC was used. Of those examined, 0.7% were anergic, 21.3 were relatively anergic, and 73 were immunocompetent. Of the 766 men, 28 were relatively anergic and 3 were anergic, whereas of the 710 women, 14 were relatively anergic (p < .001) and 8% were anergic (p < .001). The highest incidence of anergy was found in women of over 70 years (p < .001). Tuberculin was the antigen with the most positive responses, 77%, followed by Candida with 58%. Trichophyton and Proteus mirabilis were the antigens least recognized by the Spaniards studied. Major geographical variations were observed, both in the overall index for the delayed hypersensitivity response and in the response to different antigens. Catalonia revealed the highest level of anergy and the Valencia region, the lowest.
For continuous delivery of substances to conscious experimental animals a miniature osmotic pump was developed. These pumps can be implanted subcutaneously or intraperitoneally. Then with self-powered force (osmosis) substance is released with constant rate over period of 1-4 weeks (model pending). These osmotic minipumps are widely used for investigation of various substances (e. g. anesthetics, anticancer agents, catecholamines, immunomodulators, peptides, steroids). By the means of osmotic minipumps until now more than 300 substances were applied and over 4,000 papers were published on the use of osmotic minipumps in pharmacology, toxicology, oncology, etc.
Following a short review of penetration of drugs through the skin (a bilayer membrane which consists of the stratum corneum and the viable epidermis), transdermal therapeutic systems (TTS) are described. These systems are special pharmaceutical preparations capable of delivery of some drugs (e.g. very potent drugs, with narrow therapeutic index, short biological half-life) via skin under well controlled conditions. After their application drug passes directly into the systemic circulation avoiding the effect of first-pass hepatic metabolism. At the same time, their advantages and disadvantages are presented. Finally, currently existing TTS in the market containing e.g. scopolamine (motion sickness), nitroglycerin (angina pectoris), estradiol (postmenopause), clonidine (hypertension) and systems in the development are briefly reported. These transdermal therapeutic systems are considered as a new approach to improve the usage of drugs in terms of better dosage control, increased safety and easier application.
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