Changes induced by diazepam in the synaptic vesicle size of rat phrenic nerve terminals.

The effect of diazepam (Valium), administered by i.p. injection on the cross-sectional area of synaptic vesicle profiles of the endplate-rich area of the rate diaphragm was studied by electron microscopy at 15-180 min after treatment. In the dose range of 0.25-10 mg/kg, diazepam induced a significant increase of the size of the synaptic vesicles. This increase was dose-related within a certain margin, dependent on the treatment time, while the effect of each dose increased significantly with the period after treatment. At 2.5-10 mg/kg a maximum seemed to be reached at 90 min.

Glucocorticoid-induced changes in synaptic vesicles of rat phrenic nerve terminals.

The mean cross sectional area of synaptic vesicle profiles of the myoneural junction of rat diaphragm is increased significantly when rats are injected i.p. with single doses of 200 micrograms/kg dexamethasone 1/2 hr to 8 hr previously to a control injection of 0.9% NaCl. A maximum effect is observed at 8 hr after pretreatment with dexamethasone. The treatment of rats with hemicholinium-3 (300 micrograms/kg) induces a significant reduction of the vesicle size. Complete prevention of this decrease in vesicle size is already observed when the animals are pretreated with a single dose of 200 micrograms/kg dexamethasone 1/2 hr before treatment with 300 micrograms/kg hemicholinium-3. Dexamethasone in the same dose causes an optimum increase of the mean cross sectional area when it is given 1 hr before treatment of the animals with hemicholinium-3. It is concluded that glucocorticoids have direct actions in both "normal" motor nerve terminals and in motor nerve terminals with a deficient choline transport system, which may contribute to their proposed beneficial effects in certain cases of muscle weakness.

Effects of corticosteroids on the myoneural junction. A morphometric and electrophysiological study.

The mean size of the synaptic vesicles in the nerve endings of the isolated rat diaphragm was significantly increased after incubation with the glucocorticoids prednisolone (10(-5) mol/l) and dexamethasone (2 X 10(-7) mol/l). The shape of the vesicles was also changed, i.e. they became rounder. Similar increases in the mean size of the diaphragm synaptic vesicles were seen when the rats were injected with prednisolone (i.p., 2 mg/kg) and dexamethasone (i.p., 50 micrograms/kg) 2-4 h previously. The amplitude of the miniature endplate potentials was also significantly increased in diaphragms isolated from rats which had been injected with prednisolone or with dexamethasone. Changes in frequency of the MEPPs were less marked after injection of prednisolone, but a significant increase was seen after injection of dexamethasone. It is concluded that relatively low concentrations of glucocorticoids have direct effects on the motor endplate in rat diaphragm both in vitro and in vivo. We tentatively suggest that presynaptic effects may contribute to the beneficial effect of corticosteroids in deficient neuromuscular transmission, e.g. in myasthenia gravis.

The effect of a placental mammotrophin and cortisol on the ultrastructure of rat mammary gland in organ culture.

Mammary gland explants obtained from 13 days pregnant rats were cultured for 3, 6 and 9 days in the presence of serum of either virgin rats or 13 days pregnant rats. Insulin was added alone or in combination with cortisol. The way these different forms of treatment affected the ultrastructure was studied. With virgin rat serum plus insulin alone the mammary gland regressed to a lower state of development comparable to that of the virgin rat in vivo. When virgin rat serum was replaced by 13 days pregnant rat serum--which contains rat chorionic mammotrophin--the initial development was maintained, but synthesis of secretory products ceased. When cortisol was added to the virgin rat serum plus insulin, cortisol maintained the differentiated state originally present. Even some secretory activity was induced, but at a minimal level. With cortisol added to the pregnant rat serum plus insulin, the explants were stimulated to synthetize the extrude secretion products.