G. Meyniel

Presence of specific platelet-activating factor binding sites in the rat retina

The specificity of the effects of platelet-activating factor (PAF) on the electrophysiology of the retina suggests the existence of specific sites for PAF in this tissue. In this study, we report the presence of tritiated PAF ([3H]PAF) specific binding sites in membrane preparations of the retina of albino rats. The binding of [3H]PAF was saturable, specific, time-dependent and reversible. Scatchard analysis of the data revealed that the high-affinity retinal binding site possessed a Kd of 2.9 +/- 0.4 nM and Bmax of 0.85 +/- 0.16 pmol/mg protein. These values are comparable with those found for the membranous PAF receptor sites in platelets, neutrophils, lung tissue and brain. We have recently reported that PAF dose dependently modulates the b-wave of the electroretinogram (ERG) obtained from the isolated rat retina. The results of the present study suggest that such PAF-induced disturbances of the ERG may be mediated via specific receptors located in the retina.

Mechanism of the formation of X-ray-induced phosphenes. I. Electrophysiological investigations.

To explore one possible mechanism of the formation of phosphenes detected by astronauts during space flights, the x-ray stimulation of the photoreceptor cells of the eye was investigated. The albino rats retina, maintained in culture by perfusion, was used for this study. The electrophysiological response (ERG) induced by x rays was found to be identical to the one produced by a visible light stimulation. Under our experimental procedure, only a direct interaction between incident radiation and retina induced such as ERG. Irrespective of whether the experiment was performed using the isolated retina or the whole animal, we found that the ERG amplitude was proportional to the logarithm of the exposure on the retina. A comparative study indicated that, to obtain the same ERG amplitude, the incident energy on the retina must be about 5 x 10/sup 6/ times larger for x rays (E = 40 keV) than for visible light (lambda = 489 nm). The analysis of these results leads us to assume that the x rays act on the rods photosensitive molecule, rhodopsin.

Effects of platelet-activating factor on electrophysiology of isolated retinas and their inhibition by BN 52021, a specific PAF-acether receptor antagonist

The effects of (R)PAF-acether have been tested on the isolated rat retina model. Results indicate that (R)PAF-acether inhibits the electrophysiological response (electroretinogram) elicited on isolated retina by a brief light flash. Immediately after the administration of (R)PAF-acether, an irreversible decrease of the electroretinogram b-wave amplitude is observed. This effect is dose-dependent (2 X 10(-11) M, 2 X 10(-9) M, 2 X 10(-7) M) and partially inhibited by simultaneous administration of Ginkgolide B (BN 52021; 2 X 10(-5) M). These results suggest the existence of (R)PAF-acether-specific receptors inside the retina.

Metabolism of adiphenine. I. Absorption, distribution and excretion in rats and mice

1. The disposition of adiphenine labelled with 14C in two positions has been investigated in rats and mice after i.v. administration, and has been compared with that of the [14C]diethylethanolamine HCl and of the [14C]diphenylacetic acid. 2. Radioactivity in the blood declined in a biphasic manner. Biliary elimination depended upon the 14C-labelled compound administered: less than 5% dose for the diethylethanolamine moiety, 100% dose for the carboxylic moiety. Of the radioactivity appearing in rat bile, less than 1% is associated with unchanged adiphenine. 3. In preliminary metabolic studies, three major metabolites have been identified: diphenylacetic acid, diethylethanolamine and a diphenylacetic acid glucuronide. 4. Uptake by the brain of [14C]adiphenine shortly after dosing is 15 times greater than that of blood. Radioactivity is also found in the hypophysis, the adrenals and melanoid pigments, with a concn. up to 30 times greater than that found in the blood.

Comparative physico-chemical properties, biological effects, and disposition in mice of four nitrogen mustards

SummaryChlorambucil, phenyl acetic mustard, melphalan and mitoclomine are aromatic nitrogen mustard derivatives. These drugs show a fairly wide range of chemical reactivity and lipophilicity. In the series presently investigated, the more hydrophilic compounds (melphalan and phenyl acetic mustard) are the more toxic to mice and also the more active against Moloney sarcoma implanted IP in mice. No clear relation could be shown between the alkylating activity and the biological efficiency. All the compounds induce changes in DNA synthesis with differences between the timing of alterations and recovery. Nevertheless, return to pretreatment levels of thymidine incorporation is more rapid in the bone marrow and intestinal mucosa following administration of the drugs, than in tumor cells. The14C-ethyl labeled compounds was used to investigate the part of the carrying structure in their disposition in mice.

Labeling of human lymphocytes with 99mTc by means of stannous pyrophosphate. Scintigraphic applications

An original 99mTc-labeling method applied to human lymphocytes is described. This technique is based on the use of stannous pyrophosphate to reduce sodium pertechnetate. The proposed procedure has two main advantages: firstly, the labeling process takes place in a neutral and buffered medium which prevents any cellular aggregation; secondly, the labeling yield obtained is compatible with scintigraphic studies in man. The influence of each parameter on the labeling quality had been studied as well as the binding stability of the technetium fixed on cells. A systematic study of lymphocyte surface markers, before and after labeling, has led to the suggestion that the labeling process seems to affect cellular membranes, probably because of the technetium binding. Finally, scintigraphic results are presented, the study being performed on eight healthy volunteers. These results are compared with those published by other authors who used either a different radioisotope or a different labeling method.

Mechanism of the formation of x-ray-induced phosphenes. II. Photochemical investigations

Like visible light, x rays can stimulate the isolated retina and induce an action potential (ERG). To explain the modalities of interaction of incident radiation with the photoreceptor cells, we studied the modifications of the rhodopsin absorption spectrum after x irradiation. For exposures smaller than 5 x 10/sup 5/ R, a large increase in absorption in the uv part of the spectrum is observed. For exposure of 1.25 x 10/sup 6/ R, a 20% decrease is measured in the characteristic peak of rhodopsin (500 nm). In comparison to what is known for visible light, the significant bleaching of rhodopsin by x rays can account for the initiation of an ERG in the isolated retina. By analogy with the enzymatic inactivation after x irradiation, we believe that the x-ray rhodopsin bleaching could be due to an energy transfer from the opsin to the attachment site of the chromophoric group (11-cis retinal). The disorganization of this critical site of the molecule could be at the origin of the rod excitation, then of the ERG.

Mechanism of an in vitro biosynthesis of thyroid hormones from 3,5-diiodo-l-tyrosyl-3,5-diiodo-l-tyrosine: I. Manifestation of the elimination of the alanine side chain of the N-terminal diiodotyrosine

Abstract It was previously shown that 3,5-diido- l -tyrosyl-3,5-diiodo- l -tyrosine, I 2 Tyr-I 2 Tyr, acts as a precursor in the in vitro synthesis of thyroid hormones, and a mechanism of syntheis was proposed. We investigated this pathway by incubations of I 2 Tyr-I 2 Tyr with microsomal solubilized thyroid proteins. I 2 Tyr-T 2 Tyr was doubly labeled: iodinated with 131 I on the ring and tritiated either on the alanine side-chain of the N- or C-terminal diidotyrosine. It is shown that only the C-terminal alanine participates in the synthesis, the N-terminal alanine being eliminated. The result proved that I 2 Tyr-I 2 Tyr acts as precursor through a mechanism which is different from the one involving I 2 Tyr. This mechanism consists of: Schiff base formation with pyridoxal; free radical formation and cyclization; peptide bond cleavage and removal of the pyridoxal · alanine complex.

Metabolism of a new radioprotector; S-acetyl-N-glycyl cysteamine. II: Main tissue metabolites in mice bearing EMT6 tumours

1. The major tissue metabolites of the radioprotector S-acetyl-N-glycl cysteamine (I) labelled with 14C on the cysteamine group, were quantified and identified in normal tissues and EMT6 tumours implanted in mice, by chromatographic comparison with authentic reference compounds. 2. In all tissues the radioprotector undergoes rapid deacetylation and hydrolysis leading to the formation of cysteamine, which is the main metabolite involved in radioprotection. A major part of this metabolite is reversibly inactivated by binding to endogenous SH. 3. The differential radioprotection of healthy tissues versus EMT6 tumour is explained both by a lower uptake of radioprotector, and a weaker deacetylation and hydrolysis rate, in the tumour cells.

Biosynthèse in vitro d'iodothyronines à partir du diiodo-3,5-L-tyrosyl-diiodo-3,5-L-tyrosine

Abstract In vitro biosynthesis of iodothyronines from diiodo-3,5- L -tyrosyl-diiodo-3,5- L -tyrosine A comparative study of two types of in vitro synthesis of iodothyronines has been done from 3,5-diiodotyrosine and from diiodo-3,5- L -tyrosyl-diiodo-3,5- L -tyrosine (Tyr(I)2-Tyr(I)2) (equimolecular in tyrosyl rings). Incubations are made with rat thyroid gland minces in Eagles medium or with thyroid microsomal fraction. Synthesis of thyroid hormones from Tyr(I)2-Tyr(I)2 is faster and more important than from diiodo-3,5- L -tyrosine (Tyr(I)2). A mechanism of iodothyronine formation via Tyr(I)2 - Tyr(I)2 and different from the one occuring for Tyr(I)2 is suggested.