Effects of trifluoromethylaniline isomers on enzyme activities in lymphatic organs and hematology of the rat.

Three isomers of trifluoromethylaniline (TFMA) were investigated for their possible different toxic effects on the hematopoietic system in male Wistar rats. The effects of isomeric 2-, 3- and 4-TFMA were compared with those of aniline, the prototypic drug. Strong leukocytosis manifested by considerable increase in the number of all respective white blood elements was observed in the peripheral blood 1 day after the administration of 4-TFMA. In contrast, erythropoiesis, as ascertained by erythrocyte count and hemoglobin concentration, was inhibited by 4-TFMA. The determination of the ED50 revealed lymphocytes to be the most responsive elements towards 4-TFMA administration. Besides hyperemic and proliferative splenomegaly the histological changes in maturation of immunocompetent cells following the 4-TFMA administration were found also in thymus. In accord with an enhanced incorporation of [3H]thymidine, the specific activity of thymidine kinase (TdK) in spleen was increased after a single dose of 4-TFMA. Activities of the catabolic enzymes adenosine deaminase (ADA) and inosine phosphorylase (IP) decreased in both organs with the exception of IP activity in thymus. The effects evoked by the 3-TFMA isomer were regularly less pronounced, and 2-TFMA was nearly inactive.

The stimulatory effect of muramyl dipeptide (MDP) on the proliferation processes in parenchymal organs of rats.

The administration of muramyl dipeptide (MDP) in a single dose of 2 mg/kg increased markedly the utilization of 3H-thymidine for the synthesis of DNA thymine in liver, kidney and thymus, while no effect has been observed in spleen. Higher doses of MDP (5 mg and 10 mg) did not further increase the effect, but, on the contrary, in some tissues such as thymus, the effect was abolished. The repeated administration of 1 mg/kg of MDP for 7 days, contrary to single administration, had no effects. The measurement of proliferation activity in the experiment where DNA in the organs has been previously labeled with 3H-thymidine, has shown that the repeated administration of MDP (1 mg/kg) led to a more rapid decay in specific activity of DNA thymine in liver, kidney and thymus, but no effect was seen in spleen. The activities of thymidine kinase in the cytosole fraction of thymus and spleen after a single administration of MDP (1 mg/kg), are influenced in different ways. While in thymus the enzyme activity increased between 16 and 24 h, not being markedly changed in the early intervals, in spleen a significant decrease in phosphorylation of 14C-thymidine can be observed as early as 2 h after administration, and the decrease persists up to 48 h.

The topography and dynamics of cholinergic transmission in the myenteric plexus-smooth muscle preparation of the guinea-pig ileum; the effect of ketocyclazocine, a kappa opiate ligand.

Output of acetylcholine (ACh), neurogenic electromyogram (NEMG) and contractions of guinea-pig ileum preparations were studied during stimulation by high-frequency trains of impulses. Under control conditions the output of ACh per impulse after 2nd to 4th impulses during train stimulation (30 Hz) was higher by 20-40% than the level of ACh output during the first impulse. In the presence of ketocyclazocine (KTZ, 80 nmol x l-1) the output of ACh evoked by the first impulse was more effectively inhibited than that after impulses 2 to 4 so that the increase was higher (80-170%). NEMG, a direct consequence of the localized action of released transmitter (ACh), was recorded in the longitudinal muscle 4 and 10 mm aborally from the focal stimulation site. The incidence of NEMG responses was higher at the proximal than at the distal site and was proportional to the number of impulses in a train (100 Hz). At the distal site KTZ suppressed the appearance of NEMG responses to single impulses whereas at the proximal site its effect was much less; and so was its effect at either site during train stimulation. It is concluded that in the course of train stimulation, sites of transmission more distant from the stimulation focus were recruited, and consequently the secretion of ACh in succeeding impulses was enhanced. KTZ might preferentially inhibit the propagation of excitation by the very first impulse.