F. Heim

Inactivation of coenzyme a by ethanol—I: Acetaldehyde as mediator of the inactivation of coenzyme a following the administration of ethanol in vivo

Abstract Ethanol inactivates coenzyme A in liver and brain of white mice in vivo . In order to determine whether this effect is caused by ethanol itself or by acetaldehyde its metabolite the influence of ethanol and acetaldehyde on brain and liver was studied in vitro . Acetaldehyde lowered coenzyme A activity in homogenates of brain and liver. The concentrations required were 0.1–1.6 mM for brain and 1–32 mM for liver. On the other hand ethanol (20–360 mM) inactivated coenzyme A only in liver but not in brain homogenates. Since brain tissue is not able to oxidize ethanol in measurable quantities and, therefore, acetaldehyde is formed only in liver homogenates it is concluded that the action of ethanol on coenzyme A is mediated by acetaldehyde.

Influence of endogenous and exogenous cyclic 3′ , 5′ -AMP on contractile responses induced by oxytocin and calcium in isolated rat uterus

Abstract It was found that cyclic 3′ , 5′ -AMP inhibits the contractile response in isolated rat uterus induced by both oxytocin in normal and calcium ions in calcium-free Tyrode solution. In the same way endogenous cyclic AMP increased by epinephrine and theophylline in doses which were ineffective by themselves inhibits oxytocin-initiated uterine contractions. The possibility was discussed that oxytocin activates calcium to produce contractions and that cyclic AMP might be able to inactivate calcium ions in smooth muscle. The experiments reported here may furthermore confirm that the smooth-muscle relaxing effect of the catecholamines in rat uterus is mediated by cyclic 3′ ,5′ -AMP.

The influence of cyclic 3',5' -AMP on contractile responses induced by vasopressin in isolated rat uterus

Abstract In previous papers (7, 8) we have shown in the isolated rat uterus that cyclic 3, 5 -AMP inhibits contractile responses induced by oxytocin in normal Tyrode solution and by calcium ions in calcium-free Tyrode solution. Uterine contractions induced by oxytocin are also prevented by the administration of epinephrine together with theophylline or caffeine respectively, in doses which were ineffective by themselves. The synergistic effect of epinphrine and caffeine or theophylline respectively, is explained by the fact that in uterine tissue epinephrine stimulates the formation of cyclic 3, 5 -AMP by activating the adenyl cyclase theophylline or caffeine diminish the inactivation of cyclic 3, 5 -AMP by the inhibition of a specific phosphodiesterase (10, 11). In isolated rat uterus spontaneous motility and contractile responses induced by 5 mU/ml vasopressin were reversibly prevented by the addition of 0.3 mg/ml cyclic 3,5 -AMP as its dibutyrate derivative as well as by the addition of 0.001 μg/ml epinephrine together with 0.1 mg/ml theophylline. Exogenous and endogenous cyclic 3,5 -AMP in uterine smooth muscle interfered with the effect of vasopressin in the same manner as they do with the effect of oxytocin.

The anabolic effects of estrogens on mouse-liver and their inhibition by clomiphene

Abstract 0.5 mg/kg/day clomiphene-citrate given to 6-weeks old female white mice for 7 days led to a significant decrease in liver weight and RNA- and protein-content of the liver. This effect of clomiphene is not found with bilaterally ovarectomized animals of the same age. Two mg/kg estradiol applied once in form of estradiol undecylate caused a significant increase in weight, protein, RNA- and DNA-content as well as in the cellcount of the liver. This effect of exogenous estradiol is inhibited completely by 0.5 mg/kg/day clomiphene.

Der einfluss von acetaldehyd auf coenzym a-aktivität und atmung von leber- und hirnmitochondrien

Abstract Two hr after the intravenous injection of 6 mg/g ethanol the tissues and mitochondria of the liver and brain contain only 13–22 per cent of their normal content of active CoA. Acetaldehyde decreased the content of active CoA in isolated mitochondria of the liver and of the brain. In the brain mitochondria only 7 per cent of the normal content of active CoA are found in the presence of 0.5 μmoles acetaldehyde/ml. In the liver mitochondria 9 per cent of the normal content of active CoA are found in the presence of 6.1 μmoles acetaldehyde/ml. It is suggested that acetaldehyde combines with the thiolgroup of the CoA forming a semimercaptale, which does not take part in the transacetylating reaction in the test of Kaplan and Lipmann. With increasing concentrations of acetaldehyde the total respiration of the mitochondria of the liver and brain decreases. In the mitochondria of the liver the amount of acetaldehyde oxydation increases, while total respiration tends to decrease. Brain mitochondria, which contain less than 7 per cent of active CoA are able to maintain 23–46 per cent of their total respiration.

The influence of caffeine on endogenous cyclic 3',5' -AMP and uterine smooth muscle contraction induced by oxytocin.

Abstract It was found that caffeine inhibited the contractile response to oxytocin in isolated rat uterus. As it is known that uterine contractions, initiated by oxytocin are prevented by cyclic 3′, 5′ -AMP, and that this hormone may be increased by the methylxanthines theophylline and caffeine, we assumed that caffeine might increase the cellular content of cyclic 3′, 5′ -AMP to a level which is sufficient to inhibit oxytocin-induced contrations. This hypothesis has been confirmed by the result of our experiments which showed that oxytocin-induced contractions were prevented when ineffective doses of caffeine were combined with small doses of epinephrine or dibutyryl cyclic 3′, 5′ -AMP which were ineffective by themselves.

The influence of aliphatic alcohols and their halogen derivatives on the coenzyme A in the liver of mice

Abstract The effect was studied of i.v. administration of various aliphatic alcohols such as methanol, ethanol, propanol, monochloroethanol, trichloroethanol and tribromoethanol and their corresponding aldehydes on the activity ofcoenzyme A in the liver of white mice. All compounds except trichloroacetaldehyde hydrate, tribromoethanol and acetone blocked the CoA. The blocking effect reached a maximum 30–120 min after the administration of the alcohols and immediately after the administration of the aldehydes. The results support the view that CoA is not blocked by the alcohols themselves but by the aldehydes, derived from the alcohols.

Different effects of inhibition of lipolysis by nicotinic acid on the rate of clycolytic carbohydrate breakdown in brain and skeletal muscle

Abstract Nicotinic acid inhibits lipolysis in adipose tissue and leads to a reduced supply of FFA to the organs. Compensatorily the breakdown of carbohydrates is accelerated in liver and skeletal muscle. In the brain, however, which does not depend on the oxidation of FFA glycolysis is not affected by the administration of nicotinic acid.

The influence of low and high doses of theophylline on spontaneous motility and cyclic 3′, 5′ AMP content in isolated rat uterus

Abstract It was found in isolated rat uterus that 5 × 10 −4 N theophylline inhibited spontaneous contractions which were restituted by increasing extracellular calcium 4-fold. Tissue level of cyclic 3′, 5′ AMP was not affected. On the other hand, 10 −2 M theophylline elevated cyclic 3′, 5′ AMP by 170 % for at least 60 minutes. The concomitant inhibition of spontaneous uterine motility could neither be restituted by increasing calcium up to 40-fold nor by washing. It was suggested that cyclic 3′, 5′ AMP was involved in theophylline-induced uterine relaxation when the drug was administrated in high amounts able to inhibit phosphodiesterase. Small doses of theophylline (5 × 10 −4 M) were supposed to initiate relaxing effects by a calcium-antagonistic intrinsic activity.

Effect of testosterone on glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase and glutamate-dehydrogenase in mice kidneys

Abstract Studies including 18-day-old-prepuberal and 42-day-old normal or castrated male mice were performed. The results of these experiments show an increase of the weight of the seminal vesicles by 95%, an increase of the kidney weight by 34%, an increase of total protein by 45% and an increase of GPT; GOT and GLDH in the kidney by 51, 52 and 66%, resp., between 18 and 42 days after birth, due to the inductive action of endogenous testosterone. Studies with 42-day-old female mice indicate that the increase of GPT, GOT and GLDH in the kidneys after testosterone was due to enzyme induction, not affected by 200 /ug/kg and blocked by 400 /ug/kg of actinomycin D. The physiological growth and the physiological synthesis of protein, GPT, GOT and GLDH in kidneys are already suppressed by 200 /ug/kg actinomycin D. It is suggested that in the mouse kidney testosterone increases synthesis of amino acids necessary for protein synthesis via increase of GPT, GOT and GLDH.