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P Pradelles

Publications and source records attributed to P Pradelles.

At least 91 records · Page 5Linked to original sources
PubMed1987

PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TxB2 synthesis along the rabbit nephron.

The capacity of synthesis of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-PGF1 alpha, and thromboxane (TxB2) along the rabbit nephron was determined. A sensitive enzyme immunoassay was applied to isolated nephron segments, from the glomerulus to the terminal collecting tubule. The three prostaglandins and thromboxane (PG) were measured on the same samples after incubation in the presence of arachidonic acid. In the glomerulus, PGE2 synthesis (29.4 +/- 3.3 pg X glomerulus-1 X 30 min-1) represented 60% of the sum of the four PGs. PGF2 alpha and 6-keto-PGF1 alpha represented 22 and 17%, respectively, and TxB2 1.4%. The contribution of each PG to tubular synthesis was different, since at least 90% of PG synthesis consisted of PGE2. In the medullary collecting tubule (MCT), by far the major tubular site of PG synthesis, it was 809.6 +/- 140.8 pg X mm-1 X 30 min-1 for PGE2, 17.7 +/- 7.2 for PGF2 alpha, 8.3 +/- 1.9 for 6-keto-PGF1 alpha and 0.24 +/- 0.08 for TxB2. These relative proportions were roughly respected all along the tubule. Values were much lower in the convoluted and straight portions of the proximal tubule (proximal convoluted tubule: PGE2 8.2 +/- 2.0, PGF2 alpha 0.4 +/- 0.06, 6-keto-PGF1 alpha 0.26 +/- 0.04, TxB2 0.017) and the medullary and cortical thick ascending limb of the loop. They increased regularly along the distal structures of the tubule (light portion of the cortical collecting tubule (CCT1): PGE2 228.3 +/- 20.4, PGF2 alpha 4.34 +/- 0.6, 6-keto-PGF1 alpha 1.8 +/- 0.3, TxB2 0.22 +/- 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Segmental synthesis and actions of prostaglandins along the nephron.

The sites of synthesis and action of prostaglandins (PGs) along the renal tubule are examined. We focused our attention on experiments performed on well-defined nephron segments, using direct quantitative measurements of prostaglandin synthesis by radio- or enzyme-immunoassay. On the other hand, we selected, among the described effects of PGs, those obtained on precisely defined tubular segments. Among PGs, PGE2 synthesis is largely predominant all along the tubule. Its main sites of synthesis are the medullary collecting tubule and, to a lesser extent, the cortical collecting tubule and the thin limb of Henle's loop. Synthesis of PGE2 is amplified approximately tenfold in the presence of an excess exogenous substrate, arachidonic acid, compared with values measured without addition of substrate. Other eicosanoids have roughly the same distribution along the tubule as PGE2. Their rate of synthesis is, however, much less than that of PGE2, approximately 20-fold lower for PGF2 alpha and 6-keto-PGF1 alpha, and 100-fold lower for thromboxane B2 (TxB2). This contrasts with glomerular PG synthesis, where the difference between the production of PGE2 and other eicosanoids is much less marked. Most studies agree that antidiuretic hormone (ADH) and kinins augment PGE2 synthesis, whereas corticosteroids decrease it, at least in the collecting tubule. Direct effects of PGE2 have been described mainly in the medullary thick ascending limb and collecting tubule. They generally consist of a decrease in transepithelial potential difference and reabsorptive rates of water and solutes, in particular sodium and chloride. However, whatever the solute or tubular segment concerned, some studies failed to find such effects. The bulk of evidence suggests that ADH and PGs interact in kidney tubular cells. It is generally accepted that PGs antagonize the hydrosmotic effects of ADH in the collecting tubule. The mechanisms underlying these complex interactions are still under discussion: they probably involve several types of receptors and pathways for ADH action, which intervene in the modulation of both PG synthesis and cyclic nucleotides, and several types of PG receptors, either stimulatory or inhibitory to adenylate cyclase.

Animals↗
PubMed1986

Inhibitory effects of a novel platelet activating factor (PAF) antagonist (BN 52021) on antigen-induced prostaglandin and thromboxane formation by the guinea pig lung.

The effects of a new Platelet-Activating Factor (PAF-acether) antagonist (BN 52021) extracted from Ginkgo biloba leaves have been studied on the release of metabolites of arachidonic acid in IgG-dependent guinea pig pulmonary anaphylaxis in vitro. Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) were assayed using a novel ELISA technique. The release of PGE2 and TxB2 from anaphylactic lungs reached a maximum 4-5 min following the antigen challenge (about 3.2 and 31.0 ng/ml respectively) and decayed slowly during the following 25 min. BN 52021 (1, 3 and 30 micrograms/ml) produced dose-dependent decreases of the release of PGE2 and TxB2. These results suggest that there are some interactions between the release of icosanoids and PAF-acether in anaphylaxis.

Anaphylaxis↗
PubMed1986

Analysis of 6-keto PGF1 alpha, 5-HETE, and LTC4 in rat lung: comparison of GM/MS, RIA, and EIA.

The recent availability of fast and sensitive radioimmunoassay (RIA) and enzyme immunoassay (EIA) procedures to measure icosanoids has led to utilization of these techniques by many investigators. A major concern has been that techniques based on immunoreactivity may lack specificity, in particular if complex biologic fluids or tissue extracts are evaluated. The purpose of this investigation was the comparison of icosanoid measurements obtained either with EIA or RIA with those obtained by gas chromatography/mass spectrometry (GC/MS). Rats were injected with Salmonella enteritidis endotoxin, killed at various times after the injection and the lung extract assayed for 6-keto-PGF1 alpha, 5-HETE and LTC4. By EIA lung tissue was found to contain large quantities of 6-keto-PGF1 alpha after endotoxin stimulation. Comparisons made between EIA and GC/MS analysis showed good correlation between 6-keto-PGF1 alpha amounts in lung as determined by each technique. It was also determined that little purification of lung extract was needed to obtain reliable quantitation of 6-keto-PGF1 alpha, probably due to the specificity of the antibody and the large quantity of this prostaglandin produced. Crudely purified (Sep-Pak) lung extracts gave 5-HETE levels by RIA which were highly correlated with GC/MS values, but RIA values were 70% higher than those obtained by GC/MS. The presence of other components in lung extract which cross react with this 5-HETE antibody was probably responsible for the higher values obtained by RIA. LTC4 was measured by immunoassay in crude lung extracts, as well as after Sep-Pak purification and HPLC purification. LTC4 levels were identical in unpurified lung extract and after Sep-Pak purification, but decreased substantially after HPLC purification. Thus, by validating the icosanoid immunoassays, we have found that they can give accurate and reproducible results in lung tissue, although LTC4 and 5-HETE must be purified prior to analysis.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Determination of prostaglandin E2 synthesis along rabbit nephron by enzyme immunoassay.

Prostaglandin E2 (PGE2) content and synthesis have been measured in microdissected segments from the entire nephron of rabbit kidney. PGE2 was determined by an enzyme immunoassay on glomeruli or tubular segments (0.5-5 mm) either immediately after microdissection (PGE2 content) or after incubation for 15 min at 37 degrees C in the presence of arachidonic acid (PGE2 synthesis). We confirmed that collagenase used for microdissection did not modify PGE2 synthesis. A linear correlation was found between the length of tubule used in the assay and PGE2 synthesis, as well as between incubation time with arachidonic acid and PGE2 synthesis. PGE2 synthesis, expressed in picograms per millimeter tubular length per 15 min, was maximum in medullary collecting duct (517 +/- 73). High values were also found in the granular portion of distal tubule (134 +/- 22) and granular or light portion of cortical collecting tubule (199 +/- 24 and 146 +/- 10, respectively). Synthesis was lower in all other segments: 17 +/- 6 and 24 +/- 12, respectively, in convoluted and straight proximal tubule, 67 +/- 12 and 71 +/- 5, respectively, in thin descending and ascending limb, 51 +/- 9 and 23 +/- 4, respectively, in medullary and cortical thick ascending limb of Henle's loop, and 25 +/- 7 in initial distal tubule. Synthesis per glomerulus was 24 +/- 3. When the protein content of each nephron segment is taken into account, this profile was not modified, except for the thin limbs of the loop, which reached values per nanogram protein slightly higher than those of the cortical collecting tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Anti-substance P anti-idiotypic antibodies. Characterization and biological activities.

Antibodies to substance P (SP) produced in rabbits have been characterized for their specificity toward SP and some 30 SP-related peptides. For each compound, we observed a close correlation between capacity of binding to anti-SP antibodies and biological activity, namely their spasmogenic effect on guinea pig ileum in vitro and their hypotensive effect in the rat in vivo, indicating that the combining sites of anti-SP and SP receptor(s) are structurally very similar. Further immunization of five rabbits with anti-SP immunoglobulins elicited in two allotype-matched animals the production of anti-SP anti-idiotypic antibodies. These latter antibodies were found to strongly inhibit the spasmogenic action of SP on the guinea pig ileum. In contrast, they specifically enhanced, like SP, phospholipid turnover in rat parotid gland cells, a physiological function mediated through an activation of SP receptors. Immunocytochemical studies actually revealed the presence of specific membranous binding sites for anti-idiotypic antibodies on the parotid gland-dissociated cells. The anti-idiotypic antibodies described here, which thus behave either as agonists or antagonists for SP depending on the biological test, might be used as original and powerful tools not only in studies of the receptor stereospecificity but also in attempts to purify the membranous SP receptors.

Animals↗
PubMed1985

Binding of aldosterone metabolites in isolated tubular segments.

High-performance liquid chromatography (HPLC) analysis was performed on tissue extracts from whole kidney cortex (after in vivo injection or in vitro incubation with [3H]-aldosterone ([3H]A], from products bound to aldosterone receptors in cytoplasmic and nuclear fractions, and from the convoluted (PCT) and straight (PR) portion of the proximal tubule and cortical collecting tubule (CCT) isolated by micro-dissection after in vitro incubation with [3H]A (10 and 80 nM). After in vitro incubation of whole tissue, about 10% of the radioactivity corresponded to three groups of metabolites, two polar ones, which eluted earlier than aldosterone, and one less polar, which eluted later than aldosterone. When HPLC analysis was performed on bound products, after removal of free [3H]A, only one group of polar metabolites was detected (about 8% of the radioactivity) in addition to native [3H]A in the cytoplasmic and nuclear fractions. The binding of polar metabolites was nonspecific (nondisplaceable) and did not vary with incubation time and aldosterone concentration. In isolated tubules, in addition to [3H]A, an early peak of polar metabolites, corresponding to that observed in bound fractions, was present in PCT (10%) and in PR and CCT (20-25%). Other metabolites were not found in isolated tubules. We conclude the following: 1) The kidney is able to form at least three groups of aldosterone metabolites in small amounts. 2) Only one of them (more polar) was detected, as a nonspecifically bound product, in cellular fractions containing hormone-receptor complexes after removal of free [3H]A. Other metabolites were removed with free [3H]A. 3) These polar metabolites were found in both mineralocorticoid target segments such as CCT and in classically nontarget segments such as the proximal tubule. 4) The nonspecificity of the binding of polar metabolites and the absence of selective localization along the nephron suggest that they have no major mineralocorticoid action.

Aldosterone↗
PubMed1984

Highly sensitive and specific radioimmunoassays for dihydroergotoxine components in plasma.

The development of three analogous radioimmunoassay (RIA) procedures for dihydroergotoxine components is described. The antisera were produced by immunization of rabbits with immunogens obtained by coupling egg albumin to the indole group of each ergot alkaloid derivative. In each radioimmunoassay, antibodies do not cross-react more than 5% with the two other derivatives. The tracers iodinated with iodine 125 were prepared by the chloramine-T method and purified by thin layer chromatography. Both antibody affinity and high specific radioactivity of tracers allow a sensitive assay (detection limit less than 20 pg/ml) in human plasma. After high performance liquid chromatography of extracted plasma, immunoreactive materials other than those corresponding to the elution of the three dihydroergotoxine components were not detected. Two preliminary pharmacokinetic profiles obtained in dog and human for each derivative are shown.

Animals↗
PubMed1982

A new improvement of the sensitivity and specificity of radioimmunoassay for thyroliberin. Application to biological samples.

A new approach to increase the sensitivity and the specificity of a radioimmunoassay for thyroliberin (TRH) is described. The obtention of the anti-TRH antiserum used in this study has been previously reported (8): it exhibits a higher affinity for mono and di-iodo TRH derivatives. The method consists in iodinating the standards and the biological extracts with a large excess of reagents (NaI + chloramine T) under definite conditions of pH and concentrations. Mono iodo [[I125]-His2]-TRH purified by TLC was used as a tracer. This method both increases the sensitivity by 5 folds and improves the specificity by excluding or highly reducing the cross-reactivity obtained with closely related peptides. It has been successfully applied to mouse hypothalamic tissue extracts. It presents the advantage to measure low amounts of TRH in mouse tissue samples such as posterior pituitary and anterior pituitary.

Animals↗
PubMed1980

[Triiodothyronine radioimmunoassay. Comparison of the different factors between two technics (author's transl)].

Triiodothyronine concentration was determined in human serum and in thyroid extracts by two radioimmunoassay technics. Both antibodies, radioactive T3, stable T3, protein-binding-hormone inhibitors, methods used to separate the free from the bound fractions were different. Each factor from a method was substituted to the homologue of the other method. The results occasionally showed a variation of 32 p. cent in the first method and 50 p. cent in the second one. However the results gave a correct interpretation of the triiodothyronine values measured in human serum and in thyroid extracts.

Humans↗