The effects of synthetic estrogens on the metabolic clearance and production rates of estrone and estradiol.
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Biomedical subjects
Publications and source records attributed to K I Williams.
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1 The effect of perturbation of intact blood platelets with proteolytic enzymes was studied with respect to 5-hydroxytryptamine (5-HT) transport, adenine transport and intracellular Na(+) and K(+) levels.2 Leucine aminopeptidase and thrombin reduced 5-HT transport, released 5-HT from pre-labelled platelets and disturbed the gradient to monovalent cations. Leucine amino-peptidase, but not thrombin, inhibited adenine transport.3 alpha-Chymotrypsin and carboxypeptidases A and B were without effect on the parameters studied.4 Trypsin selectively reduced 5-HT transport. It did not release 5-HT from blood platelets or inhibit adenine transport.5 The action of proteolytic enzymes is discussed in terms of proteins localized in the external membrane that may function in part as membrane carriers.
1 The sensitivity of a wide range of isolated tissues to oxytocin was investigated. The longitudinal muscle strip of duck pulmonary vein proved the most suitable tissue for use with the superfusion technique, contracting to concentrations to oxytocin as low as 10 muu/ml.2 The duck pulmonary vein superfused with Krebs solution was contracted by oxytocin, the vasopressins, adrenaline, noradrenaline, 5-hydroxytryptamine, histamine and angiotensin II. Pre-treatment of the preparation with phenoxybenzamine (1-2 mug/ml) abolished the contractions to catecholamines and reduced the effects of histamine and 5-hydroxytryptamine without affecting the sensitivity to oxytocin.3 The pulmonary vein contracted when superfused with blood from an anaesthetized dog. This contraction was accompanied by a non-specific loss of responsiveness. When the pulmonary vein was superfused with Krebs solution that had been dialysed against blood the initial contraction was greatly reduced or abolished as was the loss in responsiveness.4 Oxytocin was stable in circulating dog's blood but approximately 50% was bound to plasma proteins. Oxytocin was not destroyed in the pulmonary circulation or the hind limbs. In the doses used oxytocin had a half-life of 60-90 s in the circulation of the dog under steady-state conditions. Disappearance occurred chiefly in the visceral vascular beds.
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1. Indomethacin and meclofenamate, both of which are potent inhibitors of prostaglandin synthetase, antagonized the contractor effects of oxytocin on the isolated uterus from the non-pregnant rat. Contractions induced by acetylcholine or prostaglandin F(2a) were not antagonized.2. Uteri from rats 17-22 days pregnant exhibited intermittent spontaneous contractions when used as isolated preparations. They also released prostaglandin-like activity (mainly similar to F(2a)) into the bathing fluid. Both the prostaglandin release and the uterine activity were abolished by indomethacin. Activity could be restored by addition of low concentrations of prostaglandin E(2) or F(2a).3. The release of prostaglandin F(2a)-like activity by the uteri increased dramatically on the expected day of delivery (day 22).4. The results add force to the hypothesis that the spontaneous activity of some isolated organs is due to an intramural prostaglandin generation, and that increased uterine prostaglandin production contributes to the expulsion of the foetus.
1. Stimulus-secretion phenomena in blood platelets incubated with trypsin or thrombin have been investigated.2. Secretion occurs in at least two stages: (a) induction, obtained when the platelets are incubated with proteolytic enzymes in the presence of the chelating agent EDTA, and (b) release, which occurs with the subsequent addition of Ca(2+) to the incubation medium.3. Ca(2+) was the only essential divalent cation required for release. Ba(2+) and Mg(2+) inhibited release and Sr(2+) could only partially substitute for Ca(2+).4. Blood platelets exhibited recovery from enzymic perturbation by trypsin or thrombin by a mechanism that was temperature dependent, but did not require the synthesis of new protein.5. The results are discussed in relationship to stimulus-secretion in other cells.
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