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Biomedical subjects

F Dray

Publications and source records attributed to F Dray.

At least 55 records · Page 3Linked to original sources
PubMed1986

Radioimmunoassay of [D-Trp6]-luteinizing hormone-releasing hormone: its application to animal pharmacokinetic studies after single injection and long-acting formulation administration.

A sensitive radioimmunoassay (RIA) for [D-Trp6]-luteinizing hormone-releasing hormone (LHRH) has been developed. This assay allowed measurement of the LHRH analog in unextracted plasma with a minimum detectable concentration of 10 pg/ml. Validation of plasma assays was performed through Sep-Pak and HPLC purification. The in vivo fate of the peptide was investigated in dogs after subcutaneous or intravenous injections. In both cases, the LHRH analog showed longer plasma half-life than native LHRH with an elimination half-life superior to 80 min. Long-acting formulations were tested in dogs and rats: the day following administration, [D-Trp6]-LHRH plasma level rose to 2.9-4.6 ng/ml in dogs and 0.8-3.8 ng/ml in rats. From day 4 to day 30, [D-Trp6]-LHRH plasma level followed a plateau with concentrations of 0.3-0.8 ng/ml in dogs and 0.2-0.4 ng/ml in rats. In parallel, testosterone plasma concentration was reduced to castrate level between day 4 and day 7 in dogs and was significantly lowered in rats. This sensitive [D-Trp6]-LHRH RIA will be particularly useful for the evaluation of long-acting formulations in patients with advanced prostate cancer.

Animals↗
PubMed1985

Growth hormone-releasing factor (GRF) stimulates PGE2 production in rat anterior pituitary. Evidence for a PGE2 involvement in GRF-induced GH release.

Rat anterior pituitaries were incubated over a 3-h period. Both PGE2 and GH were increased by GRF in a concentration-related manner (ED50: 3.5 nM and 6.5 nM, respectively). A significant correlation (r = 0.88, n = 127) was observed between GH and PGE2 release over the range of GRF concentrations tested. Among the five prostanoids analyzed, only PGE2 was selectively increased. Somatostatin lowered GH release, without any effect on PGE2 production. Indomethacin (Id) and Aspirin reduced significantly PGE2 synthesis and GRF-induced GH release. The inhibitory effect of Id was counteracted by addition of PGE2 to the medium. GRF and PGE2, at maximal concentrations, had a partial additive effect on GH release. The increase in PGE2 production and the reduced GH release in the presence of cyclooxygenase inhibitors suggest that PGE2 is involved in GRF-induced GH release.

Animals↗
PubMed1985

Characterization of monoclonal antibodies against prostaglandin E2: fine specificity and neutralization of biological effects.

The specificity and heterogeneity of the immune response of BALB/c mice immunized with prostaglandin E2 (PGE2) coupled to thyroglobulin was studied. All the animals (n = 50) responded to PGB2, a transformation product of PGE2. However, following repeated injections most of the animals (n = 30) were also able to respond to PGE2. Cellular hybridizations were performed and five anti-PGE2 monoclonal antibodies were isolated and analysed. They are mainly directed against the ring and the omega-chain of PGE2 but their specificity toward the alpha-chain is more limited. The association constants are greater than to 1 X 10(9) M-1. The monoclonal antibody 8E.57.71 (Ka = 1.3 X 10(10) M-1) is particularly convenient for sensitive radioimmunoassays (detection limit 25pg/ml, when iodinated tracer is used). Anti-PGE2 monoclonal antibodies were found to neutralize the specific binding of [3H]PGE2 to rat brain hypothalamic receptors and to inhibit the PGE2 induction of rat fundus muscular contraction.

Animals↗
PubMed1985

Immunological castration by a totally synthetic vaccine: modification of biological properties of LH-RH after conjugation to adjuvant-active muramyl peptide.

Recently, we demonstrated that immunological castration of male mice can be obtained by immunization with Luteinizing Hormone-Releasing Hormone (LH-RH) directly coupled to NAcMur-L-Ala-D-isoGln-L-Lys (MDP-Lys) without carrier and Freund's Complete Adjuvant (FCA) but in the presence of Polyvinyl-Pyrrolidone (PVP). In the present report, we have observed that: (a) immunization by the conjugate, LH-RH-MDP-Lys, was very effective even in absence of PVP, and this conjugate was more active than other conjugates containing MDP coupled to LH-RH fragments; (b) a strong secondary response could be observed by the administration of free LH-RH suggesting that the endogenous secretion of LH-RH might elicit a boosting effect; (c) administration of MDP-Lys coupled to LH-RH decreased the pyrogenicity of the glycopeptide; (d) such a conjugation also decreased the hormonal activity of the antigen although it enhanced its immunogenicity. These results show that a conjugate (2000 dalton) of a decapeptide hormone with a synthetic adjuvant glycopeptide can induce immunological castration in mice after administration in saline. The immunopharmacological properties of the conjugate and its conditions of efficacy suggest that such an approach could find clinical application.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Lipoxygenase products of arachidonic acid stimulate LHRH release from rat median eminence.

Exogenous arachidonic acid (AA) incubated in presence of male rat hypothalamus, shows a low rate of conversion (less than 1%) of the substrate with a major product, identified as 12-hydroxyeicosatetraenoic acid (12-HETE) by reverse phase-high performance liquid chromatography (rpHPLC) and gas chromatography-mass spectrometry (GC-MS). Furthermore, immunoreactive 12-HETE estimated after purification on rpHPLC is produced by hypothalamus slices or median eminences (MEs) incubated in absence of any exogenous precursor. The effect of 12-HETE was tested on the release of LHRH from rat MEs after a 30-min incubation and was compared to the effect of another lipoxygenase product, 5-HETE, and to the well-known stimulatory effect of prostaglandin E2 (PGE2). The three AA metabolites stimulate LHRH release. A significant stimulatory effect on LHRH release is obtained with 10(-9) M of 12-HETE and only with 10(-8) M of 5-HETE or PGE2. Furthermore, the effect of higher concentrations is different according to the eicosanoid tested. The maximal response (176% of the control) is reached with 12-HETE at 10(-8) M. No significant change is observed at 10(-7) and 10(-6) M. The response with 5-HETE is also maximal (162% of the control) at 10(-8) M but decreases significantly (only 117% of the control) at 10(-6) M. The amplitude of the response to PGE2 is larger and higher, reaching a plateau (300% of the control) at 10(-6) M. 12-HETE has no effect on somatostatin (SRIF), release, as already known for PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

[Activity of almitrine bismesylate on pulmonary hemodynamics and on the liberation of prostanoids in the lymph nodes in sheep].

Almitrine Bismesylate (0.25 mg X kg-1) was perfused for 10 minutes into the pulmonary artery of 4 sheep (40 kg) which were anaesthetized, paralysed and ventilated with 50% oxygen in air and prepared according to Staub et al (J. Surg. Res. 19:315, 1975). The preparation was followed for 2 hours baseline and for four hours after perfusion and comparisons made using analysis of variance. We noted a transitory phase marked by a peak of pulmonary vascular resistance (PVR) at 25 +/- 15 minutes due to a rise in mean pulmonary artery pressure PAP from 14 +/- 2 to 23 +/- 5 cm H2O. PO2 fell from 220 +/- 40 to 180 +/- 25 Torr. A stable haemodynamic state was attained after 90 minutes. PAP was slightly above control and PaO2 significantly elevated (230 +/- 30 Torr P less than 0.05). Left atrial pressure, PCO2, pH, and lung lymph flow did not change. The mild stable vasoconstriction associated to a rise in PaO2 at constant ventilation and high PaO2 does not suggest a straightforward role for chemoreceptors. It is compatible with redistribution of VA/Q ratios by local mediators. Lung lymph was assayed for prostanoids using radio immunological methods. A significant rise in 6 keto PGF1 alpha immunoreactivity was found posterior to the haemodynamic peak. HPLC is required to quantify further this rise.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Distribution of enkephalin in human fetus and infant spinal cord: an immunofluorescence study.

The distribution of enkephalin-like immunoreactivity in the human fetus and infant spinal cord have been studied by indirect immunofluorescence. Enkephalin-like immunoreactive fibers were detectable in the lateral funiculus of fetal spinal cord as early as 10 weeks. At the other fetal ages examined, ranging from 12 to 28 weeks, and in infant, enkephalinlike immunoreactivity was found widely distributed throughout the whole spinal cord. In fetus spinal cord several enkephalin-like immunoreactive cells were sometimes seen scattered in the intermediate gray region. Most of the labeling was, however, represented by thin, varicose, immunofluorescent fibers mainly localized in the intermediate gray regions, in the ventral horn and in the superficial dorsal horn layers where they progressively increased in number. Further, the white matter exhibited enkephalin-like immunoreactive fibers particularly in the lateral funiculus where a dense punctiform immunofluorescence could be seen. On the whole, similar patterns were also visible in infant spinal cord. Thus, the superficial layers of the dorsal horn and the intermediolateral and reticular nuclei areas displayed dense plexuses of immunoreactive fibers. In contrast, the white matter showed only little labeling. In addition, no immunoreactivity was found in fetus and infant dorsal root ganglia. Our results emphasize the wide distribution of the enkephalin-like immunoreactivity in the fetus as in the infant spinal cord and further suggest its first appearance early in fetal life, possibly at the embryonic stage.

Embryo, Mammalian↗
PubMed1984

Prostaglandins of the E series inhibit release of noradrenaline in rat hypothalamus by a mechanism unrelated to classical alpha 2 adrenergic presynaptic inhibition.

The effects of eight different prostanoid derivatives (PGs) on the in vitro release of noradrenaline (NA) from rat hypothalamic slices are reported. Prostaglandin E2 (10(-8)-10(-5) M), which does not interfere with the [3H]NA uptake mechanism, inhibited [3H]NA release induced by K+-evoked depolarization. The rank order of inhibition of release of NA for the PGs was: PGE2 greater than PGE1 greater than PGA2 greater than 16, 16-dimethyl-PGE2 greater than 11-epi-PGE2 greater than or equal to 8-iso-PGE2 greater than PGF2 alpha greater than PGD2. It has recently been shown that PGs of the E series specifically bind with a high affinity to membrane preparations of rat hypothalamus. A similar rank order was found for the activity of these PGs in displacing [3H]PGE2 from its binding sites, suggesting that the effect of PGEs on release of NA is mediated by an interaction with PGE2 receptors. Under the same experimental conditions, 10(-6) M clonidine (an alpha 2 adrenoceptor agonist) diminished, and 10(-6) M yohimbine (an alpha adrenoceptor antagonist) increased [3H]NA release, supporting the existence of alpha 2 auto-inhibition. Exposure to 10(-6) M of the alpha 1, alpha 2 adrenergic receptor antagonist phentolamine, a concentration which by itself had no effect on overflow of [3H]NA, blocked the inhibitory effect of clonidine, but failed to antagonize the inhibitory action of PGE2. Moreover, the action of clonidine and yohimbine remained unaffected when PG synthesis was blocked with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1984

Anti-inflammatory drugs, prostanoid and proteoglycan production by cultured bovine articular chondrocytes.

The effect of various anti-inflammatory drugs on the production of prostaglandins E2 and F2 alpha, 6 keto PGF1 alpha and thromboxane B2 by bovine articular chondrocytes was measured by radioimmunoassay. While indomethacin and meclofenamic acid caused a dose-dependent inhibition of all prostanoids measured, the effects of hydrocortisone and colchicine varied with respect to different prostanoids. Hydrocortisone (10(-7)M - 10(-13)M) both in the presence and absence of added arachidonic acid, resulted in an inhibition of prostaglandins E2 and F2 alpha, and to a lesser extent, 6 keto PGF 1 alpha, but TxB2 production was only slightly inhibited by the drug in the absence of arachidonic acid and markedly increased in its presence. Colchicine (10(-7)M-10(-3)M) had the opposite effect, causing an inhibition of TxB2 and stimulating PGE2 and 6 keto PGF1 alpha production. These findings suggest that certain anti-inflammatory drugs may, in addition to their action on phospholipase A2 and cyclo-oxygenases, exert potent effects at the level of the different synthetases. In order to see whether these alterations in relative prostanoid levels affected proteoglycan metabolism, the effect of anti-inflammatory drugs on proteoglycan synthesis by cultured chondrocytes was tested using 35SO4 labeling methodology. The results showed that at the concentrations tested (10(-5)M to 10(-7)M), indomethacin, dexamethasone, hydrocortisone and colchicine inhibited 35SO4 incorporation into newly synthesized proteoglycan molecules both in the presence (10(-6)M) and absence of exogenous arachidonic acid. In the same concentration range chloroquine had no effect. These results do not support the hypothesis of direct prostanoid involvement in the modulation of proteoglycan synthesis in articular cartilage.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

12- and 15-lipoxygenases in rat pineal gland.

A whole organ or a homogenate of rat pineal gland was incubated with arachidonic Acid. Two predominant metabolites were identified by mass spectrometry to be 12-hydroxy-5,8,10,14-eicosatetraenoic acid and 10-hydroxy-11,12-epoxy-5,8,14-eicosatrienoic acid. 15-Hydroxy-5,8,11,13-eicosatetraenoic acid was also formed in a smaller amount. In addition, peroxy acids appeared rapidly only at the initial stage of reaction. In various parts of rat brain the 12-lipoxygenase activity was by far the highest in pineal gland, and less than 5% of the activity was found in pituitary gland and hypothalamus.

Animals↗
PubMed1984

Decreased corticotropin-releasing factor-like immunoreactivity in rat intermediate and posterior pituitary after stalk section.

We determined the corticotropin-releasing factor(CRF)-like immunoreactivity by radioimmunoassay in intermediate and posterior pituitary lobes of stalk-sectioned and sham-operated control rats. The antigenic determinant read by the CRF antibody used was contained within the region of amino acids 26 (Gln) to 37 (Leu) of the molecule. Intermediate and posterior lobes of control rats contained similar amounts of CRF (591 +/- 78 and 487 +/- 34 pg/mg protein, respectively). The section of the pituitary stalk produced a marked decrease in CRF-like immunoreactivity in both structures. The CRF content on the intermediate lobe after stalk section was 62 +/- 17 pg/mg protein, a decrease of 90%, and that of the posterior lobe was 90 +/- 13 pg/mg protein, an 83% decrease. Our results suggest that most of the CRF-like immunoreactivity in the rat intermediate and posterior pituitary lobes is contained in nerve fibers of brain origin and support the hypothesis of a role of CRF in the release of intermediate and posterior lobe peptides.

Animals↗
PubMed1984

Noradrenaline and prostaglandin E2 stimulate LH-RH release from rat median eminence through distinct 1-alpha-adrenergic and PGE2 receptors.

Noradrenaline (NA) and prostaglandin (PG) E2 produced a dose-related stimulation of luteinizing hormone releasing hormone (LH-RH) release from incubated median eminence of adult male rats, with ED50 values of 6.10(-7) and 8.10(-8) M, respectively. The effects of some adrenoceptor agonists (10(-5) M) on LH-RH release were tested: only phenylephrine (alpha 1-agonist) stimulated LH-RH release; clonidine (alpha 2 greater than alpha 1-agonist) and isoproterenol (beta-agonist) were ineffective. Adrenoceptor antagonists (10(-6) M) were also tested: prazosin (alpha 1-antagonist) and phentolamine (alpha 1/alpha 2-antagonist) almost completely suppressed the enhanced release of LH-RH induced by NA. In contrast, neither yohimbine (alpha 2-antagonist) nor propranolol (beta-antagonist) altered this effect of NA. When tested alone, no significant effect was obtained on basal LH-RH release with any of the antagonists tested. Moreover, at concentrations that blocked the stimulation produced by NA, the adrenoceptor antagonists did not alter the effect of PGE2. Among seven PGs tested at 10(-6) M, only PGE2, PGE1, PGA2, and 16,16-dimethyl PGE2 significantly enhanced LH-RH secretion. 8-iso PGE2 weakly stimulated LH-RH secretion, whereas PGF2 alpha and PGD2 were ineffective. A direct correlation existed between the potency of these compounds to modify LH-RH secretion and to inhibit specific [3H]-PGE2 binding to hypothalamic membranes. In conclusion, these results suggest that the stimulation of LH-RH from median eminence induced by NA and PGE2 involves the activation of an alpha 1-adrenergic receptor and a PGE2 receptor, respectively.

Animals↗
PubMed1984

[The co-localization of monoamines and enkephalins in the central nervous system].

After examination of some particular methodological problems concerning the visualization of monoaminergic and "enkephalin containing" central neurones, the colocalisation of enkephalins in certains monoaminergic neurones is reported. Thus, in rat and cate raphe nuclei many serotoninergic cell bodies display enkephalin-like immunoreactivity (ELI). In the cat locus coeruleus complex most catecholaminergic neurones contain ELI. Further, the synthesis in situ of enkephalins is strongly suggested by the fact that synenkephalin-like immunoreactivity is also detected in these monoaminergic neurones. Synenkephalin is the N terminal part to the bovine medullosurrenal pro-enkephalin. Monoamine-enkephalin colocalisation has been shown in peripheral neurones and adrenal medulla. The possible functionnal significance of the coexistence of monoamine-enkephalins in neurones is discussed. In particular, some hypothetical levels of interaction are considered.

5,6-Dihydroxytryptamine↗
PubMed1983

Prostanoid profile in specific brain areas, pituitary and pineal gland of the male rat. Influence of experimental conditions.

Using chromatographic separation and specific radioimmunoassays, we were able to detect the prostanoids PGD2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha and thromboxane B2 in selected brain areas, pituitary and pineal glands of adult male rats. Our results suggest regional differences in the biosynthetic capacity of homogenates. Higher amounts were produced by the pituitary and pineal gland (33 and 28 ng/mg protein, respectively). In the hypothalamus, the median eminence was the most active part (24 ng/mg protein). The sum of the 5 prostanoids in whole hypothalamus was higher after 15 min incubation (10 ng/mg protein), than at zero time (2.7 ng) or after immediate freezing of the tissue (1.2 ng). We confirm the predominance of PGD2 after incubation of the homogenates in each of the 8 areas in the brain, pituitary and pineal gland. However, PGD2 was not predominant when the prostanoid profile was estimated immediately after homogenization or when the hypothalamus was immediately frozen in liquid nitrogen. The ratio PGD2/PGF2 alpha was 2.7, after 15 min incubation, 0.9 at zero time and 0.8 for the hypothalamus immediately frozen. Furthermore, PGD2 predominance was not observed when intact tissues were incubated without homogenization.

Animals↗