Aaron H. Anton

Ethanol and urinary catecholamines in man

By measuring the main urinary catabolites of the catecholamines and serotonin, an attempt was made to elucidate which step in the metabolism of the amines is affected by ethanol in man. There was a Significant increase in urinary norepinephrine, dopamine, and metanephrine following the ingestion of a moderate dose of ethanol. Several possible enzymatic steps in the metabolism of the catecholamines where ethanol might act are discussed. The possibility that the results may have been complicated by the effect of ethanol on other physiologic functions is also considered.

The effect of disease, drugs, and dilution on the binding of sulfonamides in human plasma

The plasma protein‐binding capacity for sulfonamides (and presumably other drugs and endogenous substances) was found to be decreased more than 10 per cent in 4 of 16 hospitalized patients. 1n other experiments it was found that a combination of drugs significantly interfered with the protein binding of sulfonamides under conditions in which each drug by itself had only slight displacing activity. The drugs decreased the binding of the sulfonamides more when diluted plasma was used, and the interference was more marked when the drugs were tested against a less highly bound sulfonamide. It is suggested that a binding defect may contribute to the incidence of adverse reactions to drugs by making available unanticipated amounts of drug. In another series of experiments the binding of sulfonamides in human plasma was determined under the following conditions: (1) dilution of plasma protein while keeping sulfonamide concentration constant, and (2) dilution of a sulfonamide‐containing solution of plasma so as to maintain a constant ratio between protein and sulfonamide. As predicted by the law of mass action, the fraction of bound sulfonamide decreased in both situations as the protein was diluted. These results may explain the erroneous conclusion of several investigators who reported that the binding of sulfonamides in human serum did not interfere with antibacterial activity.

Effect of group size, sex and time on organ weights, catecholamines and behavior in mice ☆

Abstract Male and female mice were subjected to isolation and excessive overcrowding for 1-week and 4-week periods to determine [1], what effect population density would have on organ weights and catecholamines in relationship to behavioral changes, and [2], in what manner time might influence these interactions. The only consistent significant physiologic and biochemical effects were sex-related and were not modified by changes in the environment. However, fighting behavior, a sex-related characteristic that was only elicited in the male mice, required a change in the environment, i.e. isolation, to be expressed. Thus, no measurable biochemical effect could be associated with a change in behavior.

Possible sources of error in solvent extraction procedures for catecholamines

Abstract Evidence has been presented that several naturally-occuring reducing agents may be the source of errors in solvent extraction procedures for endogenous catecholamines. By the use of the sulfhydryl inhibitor, p-chloromercuriphenyl sulfonic acid and carrying out the extraction with a pH 7.8 phosphate buffer, interference by the reducing agents was circumvented. This modified solvent extraction procedure was highly reproducible and gave the same norepinephrine, epinephrine, dopamine and dopa values as our Al 2 O 3 -trihydroxyindole procedure with a variety of tissues from several laboratory animals.

Studies on thyroid-catecholamine interactions in the isolated rabbit heart☆

Abstract Isolated atria and strips of ventricles from hyperthyroid and euthyroid rabbits were subjected to a series of pharmacologic tests in an attempt to demonstrate an interaction between the thyroid and the catecholamines on cardiac chronotropism and inotropism. These tests included dose response curves to norepinephrine and epinephrine; the use of cocaine to see whether there was a greater potentiation to norepinephrine in hyperthyroidism; dose response curves to tyramine to determine whether hyperthyroidism altered the development of tachyphylaxis to this agent; dose response curves to epinephrine in the presence of theophylline since these agents act at different sites in the cyclic-AMP system; dose response curves to mecholyl in the absence and presence of atropine to detect any hyperthyroid-induced change in cholinergic receptor sites. Our results do not support the concept of a thyroid-catecholamine interaction on cardiac chronotropism and inotropism.

The effect of reserpine on catecholamine metabolism and behavior in retarded children.

The clinical and biochemical effects of reserpine were studied in a group of retarded children whose diet, activity, and environment could be rigidly controlled. A single intramuscular iniection of reserpine induced the following significant changes in urinary catecholamines: (1) a decrease in norepinephrine and its metabolite normetanephrine, (2) an increase in epinephrine and its metabolite, metanephrine, (3) a decrease in dopa, the first catechol on the biosynthetic pathway to the other amines, and (4) an increase in vanilmandelic acid, the mator product of norepinephrine and epinephrine metabolism. The chronic administration of reserpine to two children caused a similar trend in urinary catecholamines but with some minor differences. No consistent change was observed in serotonin metabolism in either the acute or chronic study as reflected by the random day‐to‐day fluctuation in urinary 5‐hydroxyindoleacetic acid. The physiologic changes, pmticularly the onset and cessation of sedation, appeared to coincide more with changes in vanilmandelic acid, epinephrine, and metanephrine than with any of the other substances. The retarded patients excreted significantly more of all the catechols than did the normal children, but this study does not delineate the basis for this difference.

Toxicity of acids and bases after intraperitoneal injection.

Abstract Acetic acid, injected intraperitoneally, was lethal for mice housed in an incubator (37°C) and in the cold room (5°C), but not at room temperature (23°C). A dose of 4 meq/kg killed over 50% of the mice within 4 hr at the extremes of temperature, and none at 23°C. This difference in mortality was also obtained with other irritating acids and bases at the same dose, but not their salts. This effect was dose dependent with respect to the milliequivalency of injected agent. The cause of death is unknown. Poikilothermia was induced with the lethal agents at all 3 temperatures. Pretreatment of the mice with various pharmacologic agents did not prevent death. Autopsy of animals sacrificed just prior to death revealed necrosis of the mucosa and a peritoneal exudate in acid-treated animals; this pathology was judged identical at 23°C and 37°C with the same dose of acid. This pattern of mortality and poikilothermia resembles that obtained with endotoxin in mice, and may provide a simple, reproducible model for studying “endotoxic” death in mice, as well as its possible pharmacologic prevention.

Bees and biogenic amines

Abstract The honey bee ( Apis mellifera ) was tested as a model for the role of catecholamines in behavior because a stereotype social behavior and catecholamines are both present in this species. The observed differences in tissue catecholamines between the queen, drone and worker bees appeared to be more related to the stinging mechanism and sclerotizing than with the neural mechanisms of behavior. Catecholamines in bees were not affected by reserpine nor were they found in nervous tissue. Age appeared to affect catecholamine metabolism in the adult bee and probably contributed to the variability encountered. Histamine also was found in the whole bee and in the stinger apparatus.