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M Gimeno

Publications and source records attributed to M Gimeno.

70 records · Page 4Linked to original sources
PubMed1988

Purification and partial characterization of a bioactive substance from rat's vessel wall independent of prostacyclin production.

The bioactive substance from rat's vessel wall was purified by Sephadex G-75 gel filtration and by a combination of DEAE Cellulose ion exchange and Sephadex G-50 gel filtration chromatographies. Purifications of 12.5 fold and 70 fold over the initial material were achieved. PAGE of the purified material resulted in a single major band with a molecular weight estimated at 55kd-65kd. Trypsin (0.3 mg/ml) and chymotrypsin (30 mg/ml) abolished platelet antiaggregating activity. Neuraminidase (1.2 units) had no effect on platelet antiaggregating activity. This is the report of purification of aortic vessel wall antiaggregating activity independent of prostacyclin production.

Animals↗
PubMed1988

Possible mechanisms of action of ethanol-induced release of prolactin from rat anterior pituitary.

We have demonstrated previously that ethanol increases the in vitro synthesis and release of prolactin by the anterior pituitary gland. In the present study we have examined the possible role of calcium and calmodulin in the ethanol-stimulation of in vitro prolactin release from hemipituitary glands. We also investigated the effect of inhibitors of arachidonic acid metabolism on the release of prolactin induced by ethanol. In addition we studied the effect of ethanol on the release of prostaglandins and the conversion of arachidonic acid to hydroperoxides. Basal and ethanol-stimulated prolactin release was almost blocked completely by omitting calcium from the incubation medium. In vitro addition of calmodulin-blocking agents such as pimozide and trifluoperazine reduced basal and ethanol-induced prolactin release. Acetylsalicylic acid, an inhibitor of the cycloxygenase pathway, had no effect on prolactin release. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, blocked completely the release of prolactin induced by ethanol. Ethanol (5 and 10 mM) significantly increased the release of prostaglandin E2 and prostaglandin F2 alpha and the conversion of [14C]arachidonic acid to 5-hydroxyeicosatetraenoic acid. The results of this study show that ethanol increases prolactin release by a calcium-dependent mechanism. Besides, our data suggest that arachidonic acid metabolism is involved in ethanol-stimulated prolactin secretion and that lipoxygenase pathway metabolites are at least partially responsible for this effect.

Animals↗
PubMed1986

Platelet aggregating substance from mononuclear leukocytes.

Human peripheral blood mononuclear leukocytes (ML) in suspension stimulated with arachidonic acid (AA) were able to induce platelet aggregation. Shape change followed by first and second wave aggregation was the pattern of the platelet response. ML not treated with AA did not induce platelet aggregation nor did AA done at the concentration employed. The aggregating activity was not due to the ML presence, since cell-free supernatants of ML stimulated with AA induced similar platelet aggregation as the whole suspension. Aspirin incubated with ML-AA produced 65% reduction of the above aggregatory activity described while 38% and 45% reduction was obtained when ML-AA was incubated with 5, 8, 11, 14 eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA). Complete platelet cyclooxygenase integrity was necessary to obtain the second wave of aggregation induced by ML-AA, while this was not required for the first wave response. We propose that ML-AA are able to produce a platelet activating substance(s) derived from AA metabolism involving cyclo and lipoxygenase actions. It is unlikely that this substance(s) is a hydroperoxyfatty acid or thromboxane A2 (TXA2) since it is active for at least two hours once generated.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1985

Rat's vessel wall generates an antiaggregatory substance independent of prostacyclin production.

We have investigated whether the vessel wall may release or synthetize some substance able to modify the platelet function independent of prostacyclin (PGI2) production. Twenty female rats were injected with indomethacin. 18 hours after the injection animals were sacrificed and rings cut from thoracic and abdominal aorta were obtained. They were incubated in Krebs solution for different periods of time after which an aliquot from the indomethacin treated rat's aortic ring (ITRAR) was assayed on platelet aggregation induced by several agonists. The supernatant from the 40 min. incubation mixture of ITRAR released a substance which completely inhibits platelet aggregation induced by arachidonic acid (AA), ADP, epinephrine, collagen, ristocetin and thrombin. The time of appearance of the substance varied with a mean of 17 min.. It is released with and without AA stimulation. Once generated it is active for at least three hours; its antiaggregating activity remains even if it is boiled for 15 sec, incubated at 37 degrees C, or if the vessel is treated with tranylcypromine. Platelet aggregation inhibition is still evident if the supernatant from ITRAR is transferred to a platelet rich plasma (PRP) from a normal donor who had taken an aspirin 24 hours before sampling. All these results indicate that this substance released from ITRAR is not prostacyclin. Nordihydroguaiaretic or eicosatetraynoic acid which are lipoxygenase inhibitors could not modify the ITRAR's release; nor did mepacrine which is a phospholipase inhibitor. Since mepacrine does not completely inhibit phospholipase activities we cannot exclude the possibility that the substance is derived from AA. More studies are in progress to elucidate the biochemical properties of this substance.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

Rat renal medulla possess high capacity to catabolize prostaglandins.

Prostaglandin E2 is converted to 15-keto-13,14 dihydro prostaglandin E2,15-keto-prostaglandin F2 alpha and 15-keto-13,14 dihydro prostaglandin F2 alpha, by supernatants from rat kidney medulla. The main pathway for prostaglandin E2 inactivation is the combined action of 15 hydroxy dehydrogenase and delta 13 reductase enzymes. 9-Keto-reductase route constitutes a minor pathway. Prostaglandin F2 alpha is converted into 15-keto-prostaglandin F2 alpha, 15-keto-13, 14 dihydro prostaglandin F2 alpha and 15-keto-dihydro prostaglandin E2. Enzyme activities are time and substrate-concentration dependent. In the presence of an excess of substrate, rat renal medulla inactivates 40 and 56 times more prostaglandin E2 and prostaglandin F2 alpha, respectively, than the amount which is released under basal conditions. These results are in contrast to the generally accepted concept that the kidney cortex is the sole site of renal prostaglandin catabolism, and suggest, for the first time, that rat renal medulla may be a key site for the modulation of prostaglandin levels in the kidney.

Animals↗
PubMed1984

Human lymphocyte aggregation?

The purpose of the present study was to assess lymphocyte (L) aggregation. Mononuclear cells were obtained according to Boÿum. Blood was defibrinated with glass beads and laid on Ficoll-Hypaque gradients. Monocyte depletion was achieved by adherence to plastic for 18 hs. L aggregation was assayed using the turbidimetric method. When L were challenged with collagen (1-8 micrograms/ml), ADP (2.5 microM), epinephrine (1 X 10(-4) M), ristocetin (1.5 mg/ml) and bovine F VIII no aggregation could be observed. When L were stimulated by arachidonic acid (AA) (160 microM) a complete and irreversible aggregation was obtained. This effect was markedly inhibited when L were previously incubated with aspirin (40 micrograms/ml). On the other hand 5, 8, 11, 14 eicosatetraynoic acid (ETYA), a lypoxygenase inhibitor, was not able to reverse L aggregation induced by AA. Leukotriene B4, C4 and D4 were not able to induce L aggregation. When TXA2 like material from platelets and L was transferred to L preincubated with aspirin a normal aggregation response was obtained. All these results lead to the concept that the main pathway involved in L AA metabolism is probably cyclo-oxygenase. Ionophore A 23187 was not able to induce L aggregation at any concentration employed (0.1 - 100 microM) and 6 keto PGE1 could not inhibit AA induced lymphocyte aggregation.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1981

Prostacyclin (PGI2) and U-46619 stimulate coronary arteries from diabetic dogs and their action is influenced by inhibitors of prostaglandin biosynthesis.

Isolated coronary arteries from diabetic dogs presented different contractile response to U-46619 to prostacyclin (PGI2) and to arachidonic acid (AA) than those of normal dogs. The stimulatory effect of the synthetic endoperoxide analogue U-46619, was significantly higher in the diabetic condition than in preparations from normal animals. On the other hand, while PGI2 evoked a dose-dependent relaxation of normal coronary arteries, diabetic vessels were not relaxed by low concentration of PGI2 whereas higher ones produced a distinct constrictor effect. Additionally, inhibitors of prostaglandins and thromboxane (TX) biosynthesis such as corticosterone, indomethacin, acetylsalicylic acid, imidazole and L-8027, abolished the stimulatory effect of PGI2 in coronary arteries from diabetic dogs. AA relaxed coronaries from normal dogs and constricted those from diabetic animals, this action being inhibited by imidazole and L-8027. The present results suggest that: a) coronary vessels from diabetic dogs are more reactive to an endoperoxide analogue than normal preparations and b) PGI2 and AA probably contract diabetic coronary arteries via the participation of a TX like material. It is then plausible that this effect could be tentatively ascribed to the production of a prostaglandin constricting substance including also the probable generation of a TXA2-like agonist.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1980

The effect of calcium and calcium antagonists on the electrically-evoked contractile activity of isolated rat ovaries.

The effects of different calcium concentrations and calcium antagonists on the mechanical activity evoked by electrical field stimulation of isolated rat ovaries, were explored. It was observed that the force of contraction augmented and the electrical threshold diminished as the (Ca2+)0 increased. On the other hand, in the presence of calcium antagonists (Verapamil, D-600 and MnCl2) as well as in calcium-free media, the force of contraction decreased and the electrical threshold augmented. TTX, high (K+)0, propranolol and phentolamine failed to modify the responses of rat ovaries to the electrical field stimulation. The results suggest an important participation of calcium ions in the mechanisms of ovarian excitation-contraction coupling. The fast channels and intraovarian nerve endings, do not appear to be relevant for the electrically-evoked contractions of isolated rat ovaries.

Animals↗
PubMed1979

Action of glomerulopressin on smooth muscle contraction, probably mediated by the release of prostaglandins.

The effect of glomerulopressin on the increase of the contractile tension developed by isolated strips of stomach fundus, duodenum and bladder of rats, was investigated. Glomerulopressin is a glucuronide whose contractile inducing effect was destroyed by beta-glucuronidase. It was observed that glomerulopressin increases the contractile tension of these tissues, and that this action was not blocked by atropine, cyproheptadine, tranylcypromine, but was inhibited by indomethacin, suggesting that the effect of glomerulopressin action was mediated by prostaglandin release.

Animals↗
PubMedDate not supplied

Bioavailability of the iron formulated as natural ferric protein (TM/FMOA) and natural ferric protein + folic acid (TM/FMOA+FOL).

Numerous oral iron preparations are available for the treatment of iron deficiency anemia but only very few studies have been designed to measure the bioavailability of iron preparations. The aim of this assay is to determine the bioavailability of iron formulated as natural ferric protein (TM/FMOA)(FMOA=Ferrimannitol ovalbumin) and natural ferric protein with folic acid (TM/FMOA+FOL) in healthy and anemic rats. Determination of the bioavailability of iron has been carried out by studying the serum level-time curves after i.v. administration of a single dose of 1 mg iron/kg in the form of ferrous sulfate, and after oral administration of 2 mg of iron/kg in the form of TM/FMOA or TM/FMOA+FOL. The Cmax values obtained after oral administration of TM/FMOA and TM/FMOA+FOL are greater in the case of anemic rats, while the tmax values are similar in both types of animals. The bioavailability (F) is greater for the anemic rats (80% approx), and the presence of folic acid does not appear to influence the bioavailability of the iron. This bioavailability data with TM/FMOA can predict good results in further experiments in human beings with iron deficiencies.

Administration, Oral↗
PubMedDate not supplied

Inhibition of nitric oxide synthase in the hypothalamus blocks the increase in plasma prolactin induced by intraventricular injection of interleukin-1 alpha in the rat.

Injection of interleukin-1 (IL-1) into the third cerebral ventricle (3V) of conscious rats increases plasma prolactin (PRL) concentration. Nitric oxide (NO) is involved in control of corticotropin-releasing factor (CRF) and luteinizing hormone-releasing hormone (LHRH) release. Consequently, we evaluated its role in the PRL-releasing action of IL-1. In the present experiment, NG-mono-methyl-L-arginine (NMMA) (1 mg in 5 microliters of 0.9% NaCl (saline)], an inhibitor of NO synthase, or 5 microliter of saline was microinjected into the 3V of conscious, castrate male rats and blood samples were removed from jugular catheters just prior to and at 10-min intervals after injection. A second injection of NMMA or saline was given 60 min after the first. Five minutes after the injection of NMMA or saline, IL-1 alpha (0.6 pmol in 2 microliter saline), or an equal volume of saline, was injected into the 3V. Plasma PRL concentrations were increased within 10-20 min after injection of IL-1 alpha and a second pulse of PRL usually occurred at 60-70 min following its injection. The maximal increase in plasma PRL from the initial value in the animals injected with IL-1 alpha was highly significant, whereas there was no significant increase in the animals injected with NMMA plus IL-1 alpha or in the animals injected with saline or NMMA. The area under the plasma PRL curve was significantly elevated in the animals injected with IL-1 alpha above that of rats injected with NMMA plus IL-1 alpha during the first hour after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Role of nitric oxide in control of growth hormone release in the rat.

Previous experiments in this and other laboratories have revealed that nitric oxids (NO) plays a role in controlling the release of corticotropin-releasing hormone (CRH) and luteinizing-hormone-releasing hormone (LHRH). Therefore, we have investigated its role in control of growth hormone (GH) release in conscious rats by microinjecting NG-monomethyl-L-arginine (NMMA), an inhibitor of NO synthase (NOS), into the third ventricle (3V) of conscious, freely moving castrate male rats. An initial blood sample (0.3 ml) was drawn from an indwelling intra-atrial catheter just prior to injection of NMMA [1 mg in 5 microliters of 0.9% NaCl (saline)] into the 3V. To maintain the inhibitory action on NOS, a second injection of NMMA was administered into the 3V 60 min after the first. Additional blood samples (0.3 ml) were removed at 10 min intervals for 120 min. Other animals received injections of the diluent at the same times and volumes as NMMA. Interleukin (IL)-1 alpha (0.06 pmol in 2 microliters saline) was injected into the 3V immediately after the first injection of NMMA, whereas other animals received the NMMA diluent followed by IL-1 alpha. The effects of IL-1 alpha were almost identical to those of NMMA in that there was a dramatic lowering of plasma GH achieved primarily by a reduction in height of the GH pulses without a significant reduction in their number.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗