Effects of melatonin and light on porphyrin synthesis in the bovine retina, pigment epithelium and choroid.

The quantity of porphyrin synthesized in the presence of 10(-3) M delta-aminolevulinic acid (ALA) is several times higher in the bovine pigment epithelium than in the retina. Synthesis in the retina was found to be increased by illumination, whereas synthesis in the pigment epithelium was decreased if the whole anatomical unit (retina-pigment epithelium-choroid) was cultivated together. The quantity of porphyrin synthesized in the presence of 10(-3) M ALA or 10(-6) M melatonin was different when the pigment epithelium and retina were separated. The combination 10(-3) M ALA with 10(-6) M melatonin inhibited retinal porphyrin synthesis after green light adaptation, while in the pigment epithelium green light adaptation induced porphyrin synthesis. It is postulated that the light-sensitive porphyrin-haeme synthesis of the retina-pigment epithelium-choroid functional unit may serve and modulate the synthesis of guanylate cyclase for cGMP.

Effects of two microtubule-depolymerizing drugs, vincristine and vinblastine, on porphyrin production by primary neural tissue cultures.

A porphyrinogenic effect of 10(-5) to 10(-7) M Vincristine (VC) and Vinblastine (VB) was observed on primary neural tissue cultures prepared from chicken embryo brain in the presence of 10(-3) M delta-aminolevulinic acid. This effect is very pronounced in neurocyte cultures, in contrast with the documented neurite elongation defect. The microtubule disassembly by VC and VB changed the quantity of the porphyrins in the cells and medium of glial cell cultures. The correlation was studied between the depolymerization of the microtubules by VC and VB and the porphyrin overproduction of primary neural tissue cultures, the investigation also extending to 10(-7) M taxol. The direct mediation of nucleotide binding proteins of the adenyl-cyclase complex by GTP liberated from beta-tubulin during the disassembly of the microtubules is presumed.

In vitro distribution of porphyrin metabolites from 10(-3) M delta-aminolevulinic acid in primary neural tissue cultures.

The distribution of porphyrin metabolites (uro-7-6-5-copro-3-proto-heme) from 10(-3) M delta-aminolevulinic acid (ALA) in neuronal and glial primary cultures was examined by an isotopic technique. In both cell types, 8-9% of the total production (cell + medium) was found in the cells and more than 90% in the medium. In both the cells and the medium the predominant porphyrin fraction was uro + 7 carboxylic. The heme fraction of the cells was also very high. Through the exclusion of ALA-synthetase activity, the "Uroporphyria-like-model" of "hepatic porphyria" was demonstrated.

Porphyrin synthesis in primary nervous tissue cultures from 10(-3) M delta-aminolaevulinic acid in the presence of melatonin and neuropeptides.

Of the primary neuronal tissue cultures (glia cell, neuronal cells, mixed and retina cultures), the neuronal cells of (cells + medium) display the highest total porphyrin production from 10(-3) M delta-aminolaevulinic acid (ALA). In the presence of 10(-3)-10(-6) M melatonin, the quantity of total porphyrins produced by the neuronal cultures decreases in inverse proportion to the concentration. Oxytocin, lysine-vasopressin, CCK-8 sulphate ester and des-Tyr-gamma-endorphin in concentrations of 10(-5) and 10(-6) M block the porphyrin synthesis of the glia cells and display different effects on that of the neuronal cells. They enhance the total porphyrin synthesis of the cell cultures, with the exception of 10(-5) M des-Tyr-gamma-endorphin, which exerts an inhibitory effect on the glia cells.

[The effect of kryptopyrrole on the brain-activity of cats: a quantitative EEG-analysis (author's transl)]. / Die Wirkung von Kryptopyrrol auf das Gehirn der Katze: eine quantitative EEG-Analyse.

Continuing earlier investigation Z. EEG-EMG, 1976, 7, 151-156 the authors have studied the electrical activity of the cortex and subcortical regions elicited by stimulating mesencephalic reticular formation, after injection i.p. of Kryptopyrrole. The changes of activity was tape recorded and subjected to an off-line computer analysis with the method of Fast Fourier. Power spectral densities as well as auto and cross correlograms were calculated. The threshold for desynchronisation following stimulation shows a characteristic form due to the effect of Kryptopyrrole: after temporary decrease there is a marked increase. After stimulation the effect on subcortical structures in strikingly different from that of the cortex.

[The effects of kryptopyrrole on the brain of cats in the quantitative EEG-analysis (author's transl)]. / Quantitative EEG-untersuchungen über die Wirkung von Kryptopyrrol auf das Gehirn der Katzen

A frequency analyzer and a biointegrator were used to study the effect of kryptopyrrole (20, 60 or 90 mg/kg) on the cortical and various subcortical structures in cat experiments. It was found that, as regards the subcortical structures, kryptopyrrole primarily causes significant bioelectric changes in the regions of the hippocampus and amygdala; its effects in the cortex are much less marked. In the second hour of the experiment, excitation appears in the behaviour of the cats, simultaneously with an increase in area of the slow frequency regions, where-as after 4-5 hours a considerable behaviour-inhibition can be observed simultaneously with a decrease in area of the slow wave range. The experimental data confirm the behaviour-active effect of kryptopyrrole. The findings indicate that the effect of kryptopyrrole is exerted in two phases. The neurophysiological data obtained give an explanation for these contradictory behaviour changes.

Effects of kryptopyrrole on porphyrin synthesis in Bacillus subtilis 168.

We investigated the effects of exogenous 5-aminolaevulinate and kryptopyrrole, separately and together, on the porphyrin synthesis of Bacillus subtilis 168. It was confirmed that 5-aminolaevulinate increases the porphyrin content of the culture fluid in the way previously described. In comparison with the basic activity of the bacteria, kryptopyrrole enhances the amount of extracellular copro III, uro III and 5-carboxyl porphyrins. The combination of 5-aminolaevulinate and kryptopyrrole enhances the porphyrin synthesis; moreover, a more pronounced increased in porphyrin synthesis occurs if the kryptopyrrole solution used is rich in its oxidation products. In this latter case, the amount of 5,6,7-carboxylic porphyrins increases markedly along with uro III and particularly copro III, while suburoporphyrins also makes their appearance. An hypothesis is advanced to explain tentatively the increase in the porphyrin synthesis provoked by kryptopyrrole.

Genetic and biochemical analysis of haemin dependent mutants of Bacillus subtilis.

Numerous porphyrin auxotrophic mutants have been isolated from the 168 trpC2 strain of Bacillus subtilis by selection with streptomycin. Some of them could be supplemented with ALA while the majority grew only in the presence of haemin. Among the latter strains, the syntropism test allowed to distinguish two groups different in phenotype, viz., feeders accumulating ALA and non-feeders accumulating instead of ALA other porphyrin intermediates. On the basis of transductional studies, feeders and non-feeders could be divided into two and four groups, respectively. Biochemical investigation revealed that, with one exception, one enzyme of the porphyrin biosynthesis was coordinated to each hem locus. The following genes were identified:hemB yields ALA-dehydrase;hemC yields PBG-deaminase; hemE yields uroporphyrinogen decarboxylases; hemF yields coproporphyrinogen oxidase; hemG yields protoporphyrin-iron-chelatase.