Common Site Of Action Research Articles

Stereospecific regulation of plant glucan synthetase in vitro

Glucan synthesis from uridine diphosphate glucose (UDP-glucose), mediated by particulate-bound enzyme from a variety of plants, is stimulated by a number of sugars and glycols. Glucose and glycerol appear to have a common site of action. Erythritol competitively inhibits glycerol-stimulated glucan synthesis. A marked disparity in stimulation by optical isomers of arabitol is indicative of a stereospecific activator mechanism.At 50 °C, particulate-bound β-1,3-glucanase hydrolyzes most of the glucan previously formed at 22 °C in the presence of glycerol, leaving a resistant glucan residue. Glucan formed in the absence of glycerol was not hydrolyzed.The supernatant above the 12 000 × g particulate fraction contains a heat-stable stimulator, and a heat-labile inhibitor, of glucan synthesis.

Estrogenic and antiestrogenic effects of clomiphene, MER-25 and CN-55,945-27 on the rat uterus and vagina.

The estrogenic effects of compounds which also possess antiestrogenic activity, MER-25, clomiphene and CN-55,945-27, were compared with those of 17β-estradiol in ovariectomized rats. Increases in uterine glycocogen, glucose, per cent water, and vaginal glycogen were noted with single doses of all the compounds. The maximal glycogen response to the inhibitors was about of that induced by estradiolestradiol at the doses employed. The 3 antagonists also markedly inhibited the 6-hr increase in glycogen, glucose and per cent water due to estradiol when they were given in multiple doses prior to estradiol treatment. These results suggest that MER-25, clomiphene, and CN-55,945- 27 are competitive inhibitors of estrogen at a common site of action. (Endocrinology 82: 69, 1968)

The Effect of Bradykinin, Kallidin and Eledoisin upon the Pulmonary Vascular Bed of an Isolated Blood‐Perfused Rabbit Lung Preparation

AbstractThe polypeptides bradykinin, kallidin and eledoisin were more potent vasoconstrictors in an isolated blood‐perfused rabbit lung preparation than were noradrenaline, 5‐hydroxytryptamine and histamine. Acetylcholine was, however, even more potent as a vasoconstrictor in the preparation than were the three polypeptides. The polypeptides were apparently not acting via a liberation into the perfusate of circulating noradrenaline, 5‐hydroxytryptamine or histamine. Bradykinin and kallidin both showed some tachyphylaxis, and also cross‐tachyphylaxis, indicating a common site of action. Eledoisin showed a very marked tachy‐phylaxis, but no cross‐tachyphylaxis towards the two other peptides, indicating a different site of action from that of bradykinin and kallidin. Phenylbutazone and sodium salicylate reduced the responses to plasma kinin injections by some 30–60 per cent, but nonspecifically, as e.g. 5‐hydroxytryptamine responses were reduced to the same extent.

THE UPTAKE OF LOCALLY APPLIED (6:7-3H)OESTRADIOL-17-BETA BY THE VAGINA OF THE OVARIECTOMIZED MOUSE.

SUMMARY Locally applied [6:7-3H]oestradiol was taken up rapidly by the vagina, at a rate similar to that of oestrone. Levels of radioactivity in the tissue reached their highest value 1–3 min. after application, and thereafter dropped slowly to reach 20% of the injected dose at 12 hr. This is in contrast to the behaviour of oestrone, the tissue levels of which fell rapidly over the first ½ hr. It is suggested that this difference accounts for the relative biological activity of the two hormones in the vagina, and results from varying affinities for receptor sites associated with the initiation of vaginal growth. Evidence is presented that oestrone, oestradiol and oestriol have a common site of action. Dimethylstilboestrol (DMS) converted the retention pattern of oestradiol to one resembling that of oestrone, and it is suggested that this involves blocking of receptor sites. The results are discussed in relation to the mode of action of oestrogens.

Effects of Herbicides and Related Chemicals on Oxidation and Phosphorylation by Isolated Soybean Mitochondria.

Herbicides have been shown to affect many diverse processes in plants. Respiratory responses, however, are general, and the idea that a common site of action exists somewhere in the oxidation or phosphorylation systems would seem to be a good working hypothesis (11). In recent years evidence has accumulated that the enzymes involved in aerobic plant respiration and phosphorylation are located in discrete cytoplasmic particles called mitochondria (5, 8). The reactions mediated by these enzymes may be carried out in vitro by properly isolated particles. Although isolated plant particles would appear to be favourable for the study of the effects of herbicides on respiratory enzyme systems, only one referenee (3) to such an investigation has been found. The experiments reported here were carried out with an in vitro particulate system with the hope of further elucidating the mechanism of action of certain herbicides and related chemicals in vivo. The particles used were isolated by differential centrifugation from etiolated soybean hypocotyls and were shown to have oxidative and phosphorylative activities similar to those from mung beans (10). In most experiments treatments consisted of the addition of various concentrations of herbicide or other chemical to Warburg flasks containing the reaction mixture. The effect of the chemical on oxygen uptake by the soybean particles was then expressed as percentage of control (table I). Some of the chemicals tested inhibited oxygen uptake only when added at relatively high concentrations. This suggests an osmotic effect, and probably such an explanation is correct for chemicals that inhibited only at concentrations of 0.1 M or higher, such as sodium chlorate (cf. sodium chloride, table I). Others including 2,4-dichlorophenoxyacetic 1 Received August 23, 1956. 2 Journal Paper No. J-3013 of the Iowa Agricultural Experiment Station, Ames, Iowa. Project No. 944. 3 This research was supported by a Fellowship grant from the Standard Oil Company of Indiana. 4 Present address : Department of Botany, Ontario Agricultural College, Guelph, Ontario, Canada.