P. Dal Pra

Plasma acth and cortisol levels in benzodiazepine treated rats

Summary In rat a single i.p. administration of various benzodiazepines (bromazepam, chlordiazepoxide, clonazepam, diazepam, flunitrazepam, flurazepam, medazepam, nitrazepam) at doses equivalent to those employed in humans brings about a clear-cut decrease of ACTH levels in plasma, without changes in plasma cortisol levels. The repeated administration (0.5 mg/kg every 24 hours for 4 days) of diazepam, in addition to a decrease of plasma ACTH levels, brings about a decrease in plasma cortisol levels.

L-2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACID AND GLUTATHIONE IN HUMAN IMMUNODEFICIENCY VIRUS

Abstract The administration of L-2-oxothiazolidin-4-carboxylic acid (OTC) and glutathione (GSH) to modulate total GSH levels was examined in 24 men with human immunodeficiency virus (HIV) and 10 healthy HIV-seronegative control subjects. The mean blood GSH concentration in the control subjects was 1.65 ± 0.287 μmol/ml while that in the HIV-seropositive patients was 0.61 ± 0.248 μmol/ml. The oral administration of OTC 25 mg/kg and the intramuscular administration of GSH 800 mg/day in the HIV-seropositive subjects markedly increased the total GSH levels. These results suggest that a systemic decrease in GSH levels could be one of the factors involved in the immunodeficiency of HIV-seropositive patients.

Effect of various antiinflammatory drugs on plasma acth and cortisol levels in rats

Summary Various antiinflammatory drugs have been injected i.p. to rais at doses equivalent to the maximal doses used in humans and plasma ACTH levels have been measured by a radio-bioassay. After acetylsalicylic acid, diclofenac and ibuprofen administration, a drop in plasma ACTH levels is observed, without a concomitant change in plasma cortisol levels. Small decrease in plasma ACTH is observed with ketoprofen, pirprofen and oxyphenbutazone; no change or a small increase is seen after azapropazone, naproxen, phenylbutazone and benzydamine. Repeated administration (five times 10 mg/kg every 24 hours) of acetylsalicyclic acid brings about a steady decrease of ACTH, which resumes its value after 48 hours. No change in cortisol levels are seen concomitantly to the short term drop in ACTH levels and small changes are seen in repeated administration of acetylsalicylic acid.

Indomethacin and sulindac inhibition of acth stimulated cortisol release from adrenal glands in vitro

In slices of adrenal glands of guinea pig added ACTH (from femtograms to picograms levels) stimulates cortisol synthesis and release. This effect is antagonized in a non-linear competitive way by indomethacin (KE = 1.3 .10(-7)) and by sulindac (KI = 6.9 .10(-10)); indoprofen is a very weak antagonist. A number of other non-steroid antiinflammatory drug are ineffective as antagonists of ACTH.

Femtogram determination of ACTH by bioradioimmunoassay.

Summary Adrenocorticotropic hormone (ACTH) added to slices of guinea-pigs adrenal glands stimulates cortisol synthesis. By assaying by radioimmunoassay the cortisol released into the suspending medium it is possible to determine femtogram levels of ACTH in biological fluids.

Effect of ACTH, β-endorphin, morphine and naloxone on the release of cortisol by isolated adrenal glands

The release of cortisol (determined by RIA) from isolated slices of adrenal glands of guinea pigs is stimulated by ACTH, by beta-endorphin, and by morphine in a concentration-dependent way; naloxone gives a small stimulation which is not related to its concentration. Naloxone inhibits the effect of ACTH (1.11 X 10(-11) M) in a competitive manner with an IC50 of about 3.10(-9) M. Also morphine and beta-endorphin inhibit the effect of ACTH, but not in competitive manner. Naloxone (10(-9)-10(-7) M) gives a concentration-related inhibition of the increase of cortisol release produced by morphine (10(-8) M) and by beta-endorphin (1.44 X 10(-10) M). These data suggest a similarity in the conformation of ACTH, beta-endorphin, morphine and naloxone towards the binding sites of ACTH of the guinea pig adrenal glands.

Effect of ouabain on the kinetics of atp hydrolysis in the guinea pig heart

Summary In electrically driven strips of guinea pig right ventricle suspended in Tyrode with added ATP (1 mM), ouabain (10 −7 and 10 −5 ) inhibits the steps of the sequence ATP→ADP→AMP and the disappearance rate of this last compound. A similar effect of ouabain (10 −5 and 10 −4 ) is observed in homogenates of guinea pig heart with added ATP (5 mM).

Effect of morphine and naloxone on the levels of acth and beta-endorphin in plasma, brain and pituitary of rats

The effect of i.p. administration of morphine (25 mg/kg) and of naloxone (50 mg/kg) on the levels of ACTH and beta-endorphin in plasma, in brain and in pituitary has been studied in rats. An opposite effect morphine and naloxone is seen in plasma ACTH with an increase elicited by morphine and a decrease produced by naloxone. Small changes are seen in plasma levels of beta-endorphin as well as in ACTH and in beta-endorphin levels in brain and in pituitary. To every change in ACTH levels in plasma an opposite change in ACTH brain levels is observed.

Kinetics of ouabain outflow from isolated frog heart evaluated by the dose-effect relationship and compared to the outflow kinetics of the tritiated drug

In isolated frog hearts the kinetics of ouabain disappearance from the receptor biophase(s) related to the effect has been calculated from the relationship between ouabain concentration and its inotropic effect. When 10(-4) - 10(-5) M ouabain is added to the heart, the kinetics is biexponential with a fast component with a time constant of 1.7 min-1 and a slower component with a time constant of 0.28 min-1. The kinetics of the washout curve of 3H ouabain (added together with unlabelled drug, shows, in addition to the slow exponential component of about the same time constant (0.2 min-1) previously seen, another component with a 10 times longer time constant, related to ineffective drug concentrations and corresponding to a washout from aspecific sites. The kinetics of ouabain outflow from compartments which are related to the effect elicited by 10(-4) - 10(-5) M concentrations is formed mainly by two steps with time constants of 1.7 min-1 and 0.28 min-1.