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Biomedical subjects

E Borda

Publications and source records attributed to E Borda.

At least 91 records · Page 5Linked to original sources
PubMed1986

Characterization of (-)-(3H)-DHA binding to intact mouse lymphocytes: effect of experimental autoimmune orchitis on beta-adrenoceptor expression.

Autoimmune orchitis induced an increment in the beta-adrenoceptor populations in intact mouse lymphocytes, depending on their source. Characterization of (-)-(3H)-DHA specific binding to intact normal cells indicate that thymic cells do not have the ability of binding a beta-adrenergic ligand. In contrast, spleen and lymph node cells showed a homogeneous population of beta-adrenergic receptors. (-)-(3H)-DHA binding was a rapid, reversible and stereospecific process. Competition experiments indicated the order of potency of the agonists and led to their definition as being of the beta 2-adrenoceptor subtype. Saturation assays and Scatchard analysis indicated a single class of binding sites (being free of allosteric or cooperative interaction) in both control and immune cells. However, spleen and lymph node cells from mice hyperimmunized with testicular preparations showed a marked increase in the number of beta-adrenoceptor sites with no changes in chi d. These results emphasize the use of lymphocytes possessing a homogeneous population of beta 2-adrenoceptors as an easily available model for monitoring beta-adrenoceptors in disease.

Alprenolol↗
PubMed1986

Role of beta 2-adrenoceptors in the biological effect of autoimmune orchitis spleen cells.

Autoimmune orchitis induced an increment in beta 2-adrenoceptor populations in intact mouse spleen lymphocytes. Normal and autoimmune lymphocytes incubated with soterenol increased the mechanical response of isolated atria. Autoimmune cells were more effective than normal cells in inducing this response. Soterenol or spleen cells alone did not modify the contractility at the concentration used. Inhibitors of beta 2-adrenoceptors of spleen cells completely blunted the reaction between soterenol and lymphocytes, while when atria were exposed to butoxamine, mechanical activity induced by soterenol plus lymphocytes was not affected. Cell-free supernatants of lymphocytes exposed to soterenol elicited the reaction in the same way as soterenol-treated lymphocytes. Direct contact of cells with the assay organ was not necessary. Inhibitors of cyclooxygenase on lymphocytes blocked the reaction of soterenol-treated lymphocytes on atria, while inhibitors of lipoxygenase(s) completely blocked the reaction of atria exposed to soterenol-stimulated lymphocytes or supernatants. These results suggest that soterenol reacts with beta 2-adrenoceptors of normal and autoimmune cells. From this reaction, soluble factors are released that in turn trigger stimulation of the atrial contractility as a consequence of the release of oxidative products of the lipoxygenase(s) pathway of arachidonic acid from atria. The high activity of atria in the presence of autoimmune spleen cells is probably related to the increment in number of beta 2-adrenoceptors of these cells.

Adrenergic beta-Agonists↗
PubMed1986

Potential role of mononuclear cells infiltration on the autoimmune myocardial dysfunction.

In autoimmune myocarditis significant alterations in contractility when the heart is studied in vitro could be demonstrated. The isolated atria from mice hyperimmunized with heart exhibited tachycardia, decrease in contractility and dysrhythmia. Spleen lymphocytes from mice with autoimmune myocarditis, can react in vitro with spontaneously beating normal atria inducing dysrhythmias and negative inotropic effect. The alterations in contractility of normal atria induced by immune cells, resemble those observed in atria from animals with autoimmune myocarditis. The use of pharmacologic inhibitors strongly suggests that the cardiac dysfunction is generated by the release of endogenous SRS-A as a result of the hyperimmunization with heart. The possibility that autoimmune lymphocyte can influence the contractile behavior of the heart is interesting and could provide some evidence for the role of lymphocytic infiltration in the mechanism operating in primary and specific myocarditis.

Animals↗
PubMed1985

Modification of the contractile activity of isolated rat atria by lectin-activated T-lymphocyte subsets.

We had previously shown that human T-lymphocytes (ERFC) that had been activated for a short time with phytohemagglutinin (PHA) produced positive inotropic and chronotropic effects on spontaneously beating rat atria (Sterin-Borda, L., et al., Naunyn Scmiedeberg's Arch. Pharmacol. 324, 58, 1983). In this study, we first prepared T4-rich (T4) and T8-rich (T8) cells from ERFC by selective lysis with OKT4 and OKT8 monoclonal antibodies and rabbit complement. Then, we tested the effect of PHA-stimulated T4 (PHA-T4) and T8 (PHA-T8) on beating rat atria. PHA-T4 cells stimulated the tension and the frequency of contraction of isolated rat atria by a mechanism that involved the generation of the slow reacting substance of anaphylaxis (SRS-A), since both 10(-5) M nordihydroguaiaretic acid (NDGA) and 10(-7) M FPL-55712 were effective inhibitors. On the other hand, PHA-T8 cells decreased the tension of beating atria. Indomethacin (10(-6) M) could not block the depressor effect. Cell-free PHA-T4 supernatants reacted with the heart tissue similarly to whole PHA-T4 cells. Since NDGA or FPL-55712 treated organs did not respond to active PHA-T4 supernatants, the lipoxygenase system of the auricles seems to be required for the reaction and the active metabolites appear to derive mainly from the heart. Our results suggest that PHA-activated "helper/inducer" cells release soluble factors that can in turn trigger the lipoxygenase metabolic pathway of arachidonic acid in the heart, generating the active leukotrienes responsible for the positive inotropic and chronotropic effects.

Animals↗
PubMed1985

Alloimmunization-induced changes in thymocytes' prostaglandin levels: a signal for the induction of biological activity.

The effect of BALB/c anti C3H non-adherent thymocytes on the spontaneous activity of isolated C3H mouse atria was studied. Immune non-adherent thymocytes alone induced negative inotropic action, while macrophages alone did not have any effect. The same kind of collaborative effect between both cells is described. Cell-free supernatants obtained from non-adherent immune cells incubated with C3H myocardium induced the same biological activity than immune non-adherent thymocytes indicating that a soluble factor is involved. Inhibition of non-adherent thymocytes' cyclo-oxygenase activity prevented the negative inotropic effect of immune cells or cell-free supernatants. In contrast, when the inhibitors were applied upon myocardium did not modify the response. Supernatants from immune thymocytes plus myocardium, release higher amount of PGE series than those from non-immune thymocytes. It is proposed that non-adherent thymocytes are able to synthesize and release PGE series upon recognition of alloantigens expressed by atria cells; which in turn triggers the negative inotropic effect.

Animals↗
PubMed1985

Prostaglandins, cyclic AMP production and biological activity of alloimmune thymocytes.

The effect of alloimmunized non-adherent thymocytes on the spontaneous activity of the mouse atria was studied. BALB/c anti C3H non-adherent thymocytes induced negative inotropic effect on C3H atria. Cell-free supernatant from non-adherent thymocytes induced the same biological activity. This activity was blunted by the inhibition of non-adherent immune thymocytes' cyclo-oxygenase activity. PGE was present in higher amounts in free-cell supernatant from BALB/c anti C3H thymocytes plus C3H atria than in those from non-immune thymocytes. Intracellular levels of immune thymocytes cAMP are raised in comparison with those of normal thymocytes. It is proposed that alloantigen stimulates non-adherent thymocytes, increasing intracellular levels of cAMP and PGE. Immune thymocytes, release PGE upon recognition of the alloantigens expressed in the atria and this triggers a negative inotropic effect. The increment in immune thymocyte cAMP appears to be associated with the activation of thymocytes cyclo-oxygenase activity by alloimmunization.

Animals↗
PubMed1985

The effects of norepinephrine and acetylcholine in the vas deferens from normal and diabetic rats: influence of ouabain and verapamil.

In vas deferens from acute and chronic diabetic rats a hypersensitivity to norepinephrine and acetylcholine was observed. The hypersensitivity to norepinephrine was markedly reduced by treatment with ouabain or verapamil. On the contrary, the response to acetylcholine was not modified by ouabain in the same concentration, but was inhibited by verapamil. Under normal conditions, ouabain and verapamil did not modify the stimulatory effect of either norepinephrine and acetylcholine; however increase of extracellular potassium concentrations potentiated the action of norepinephrine. The results suggest that ouabain-sensitive (Na+ + K+)ATPase exists in the rat vas deferens. In diabetic animals, the supersensitivity to norepinephrine is associated with an increase in membrane permeability to calcium ions that could be related to hypersensitivity of the enzyme. Under normal conditions it is possible to mimic the hypersensitivity to norepinephrine through an increase in the extracellular potassium concentration.

Acetylcholine↗
PubMed1984

Variable inotropic effect of immune cells on mice atria--participation of metabolic products of arachidonic acid.

The effect of BALB/c anti CF1 lymph node cells and thymocytes on the spontaneous activity of isolated CF1 mouse atria was studied. Immune lymph node cells induced opposite effects depending on the number of immunizations. Immune lymph node cells from mice which received two immunizations decreased the contractile tension of the atrium, whereas, cells from mice exposed to three and five immunizations strongly increased the tension. Immune thymocytes induced only negative inotropic action and this effect did not depend on the number of immunizations. Indeed, it was similar after two, three or five immunizations. Control normal lymph node cells or thymocytes from BALB/c or CF1 mice had no effect on CF1 atria. Furthermore, BALB/c anti CF1 cells had no effect on BALB/c atria. Inhibitors of cyclooxygenase activity prevented the negative inotropic influence of immune thymocytes and lymph node cells seen after two immunizations. In contrast, inhibitors of the lipoxygenase pathway abolished the positive inotropic action induced by lymph node cells obtained after three and five immunizations. Cell-free supernatants of lymph node cells from animals receiving five immunizations, stimulated the contractile activity of atrium, while those from thymocytes inhibited it, indicating that soluble factors are generated by contact of immune cells with the myocardium. It is proposed that upon recognition of alloantigens expressed by atrial cells, lymph node cells and thymocytes are activated and release either arachidonic acid metabolites or some factor(s) that induces this release by other cells, which in turn triggers different effects in myocardial tissue depending on the set of cells involved in the primary immune response.

Animals↗
PubMed1984

A circulating IgG in Chagas' disease which binds to beta-adrenoceptors of myocardium and modulates their activity.

It has been shown that sera from chagasic patients with positive EVI serology could act in co-operation with complement or normal human lymphocytes as a partial beta-adrenoceptor agonist increasing the contractile tension and frequency of isolated rat atria, as occurs with IgG purified from chagasic serum. In this paper we demonstrated that IgG present in chagasic patients sera could bind to the beta-adrenoceptors of the heart and stimulate contractile activity of myocardium. The positive inotropic and chronotropic effect could be blocked by the specific beta 1-adrenoceptor antagonist but not by the beta 2-adrenoceptor antagonist. Chagasic IgG inhibited the binding of (-) 3H-DHA to beta-adrenoceptors of purified rat myocardial membranes behaving as non-competitive inhibitors. The reactivity of chagasic serum or IgG with beta 1-adrenoceptor was lost after absorptions with turkey red blood cells. In contrast, guinea-pig red blood cells were unable to remove the beta 1 reactivity of chagasic serum or chagasic IgG. This supports the specificity of beta 1-adrenoceptors of the chagasic IgG and the independence of beta 1-adrenoceptor reactivity in relation to the EVI system. Clinical specificity of the beta 1-adrenoceptor reactivity seems rather high in Chagas' disease since it was lacking in 14 individuals with other cardiopathies, such as ischaemic and rheumatic heart disease, even after heart surgery.

Animals↗
PubMed1984

Alloimmune IgG binds and modulates cardiac beta-adrenoceptor activity.

Purified IgG from murine alloimmune sera directed against class I products from the major histocompatibility complex of the mouse, could bind to the beta-adrenoceptors and stimulate contractile activity of myocardium. Immune IgG inhibited the binding of (-) 3H-DHA to beta-adrenoceptors of mouse myocardial membranes behaving as a competitive inhibitor. Moreover, immune IgG induced positive inotropic and chronotropic effects on isolated mouse atria. These effects could be blocked by beta-adrenoceptors antagonists. Data prove that immune IgG directed against specific alloantigens are able to recognize the beta-adrenoceptors and mimic the stimulation of the beta-adrenoceptor agonist.

Animals↗
PubMed1984

Stimulatory effect of lymphocytes from Chagas' patients on spontaneously beating rat atria.

The aim of this work was to study the effect of lymphocytes from individuals infected with Trypanosoma cruzi (Chagas' patients) on the contractile behaviour of living heart tissue. Chagas' lymphocytes (ChL) reacted with isolated rat atria preparations increasing the isometric development tension (IDT) and frequency of contractions (FC) in a dose-dependent manner. The maximal stimulatory effect was reached after 30-40 min of contract. In contrast, normal lymphocytes (NL) did not alter the basal IDT and FC values. beta-adrenergic antagonists, anti-histamine agents and inhibitors of the synthesis and action of arachidonic acid (AA) products were used to study the mechanisms of the reaction. (-)-propranolol (10(-7)M) and pyrilamine (10(-6)M) had no effect ruling out the participation of beta-adrenergic agonists or histamine. However, indomethacin (10(-6)M) and acetylsalicylic acid (1.8 X 10(-4)M) enhanced the effect of ChL. Inhibitors of the lipoxygenase pathway (5,8,11,14-eicosatetraynoic acid, 10(-7)M; nordihydroguairetic acid, 10(-5)M) and FPL55712, an antagonist of one of its terminal products: the slow reacting substance of anaphilaxis (SRS-A), abolished the reaction. Therefore, a fundamental role for SRS-A in the production of the stimulatory effect is postulated. Lymphocytes of the T cell lineage (E rosette forming cells, ERFC) are the effector cells involved in this reaction, whereas non-rosetting ChL depressed IDT. T ascertain if effector cells could be replaced by soluble factors, ChL were reacted with homogenates of rat atria and the cell free supernatants were added to beating rat atria. Positive ino- and chronotropic effects were obtained, indicating that soluble factors generated during the reaction can substitute for the intact effector cells. On the other hand if the effector cells were purified from Chagas' patients that had been treated 1 month to 6 years before the assay with trypanocidal drugs (3-methyl-4-(5'-nitrofurfurylidene-amino)-tetrahydro-4H-1, 4-tiazine-1, 1-dioxide, nifurtimox or N-benzyl-2-nitro-imidazolacetamide, benznidazole) only depressor effects were found. The depressor inotropic action of lymphocytes from treated patients (tr-ChL) was abolished with indomethacin and acetyl salicylic acid indicating that products of the cyclooxygenase pathway of AA were involved. While this work provides additional evidence for the hypothesis that lymphocytes from T. cruzi infected patients may react with heart tissue and alter its contractile behaviour, the results should not be extrapolated to the in vivo situation.(ABSTRACT TRUNCATED AT 400 WORDS)

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1983

Effect of phytohemagglutinin-stimulated human lymphocytes on isolated rat atria. Participation of lipoxygenase products of arachidonic acid metabolism.

The effect of phytohemagglutinin (PHA) stimulated human lymphocytes on the contractile activity of isolated rat atria was studied. Increased isometric developed tension (IDT) and higher frequency of contractions (FC) were observed shortly after contact of PHA-activated lymphocytes with spontaneously beating rat atria. Since pre-exposure of the lymphocytes to PHA was not necessary and the pharmacologic effects were demonstrated immediately after addition of the lectin, division of the effector cells as a requisite for their action was excluded. Experiments performed with the antibiotic crystallized from Streptomyces chartreusenis, Ca2+-ionophore A-23187, yielded similar effects. Lymphocyte fractionation studies showed that T-lymphocyte-rich and T-lymphocyte-depleted cell fractions had opposite effects on IDT and FC. The inotropic and chronotropic effects were not modified by (-)-propranolol or antihistaminics. Inhibitor of the synthesis of prostaglandins enhanced the action of PHA-activated lymphocytes but inhibitors of the lipoxygenase pathway: 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) prevented the increment of IDT and FC. Also, FPL55712, an antagonist of SRS-A abolished the positive inotropic and chronotropic effects of PHA-activated lymphocytes on rat atria. Therefore, a central role for SRS-A in this reaction is suggested.

Animals↗
PubMed1983

Lipoxygenase inhibitors alter aggregation and adhesiveness of human blood platelets from aspirin-treated patients.

The influences of arachidonic acid (AA) and of inhibitors of lipoxygenases (eicosatetraynoic acid-ETYA- and nordihydroguaiaretic acid -NDGA-) on platelet aggregation evoked by collagen or adenosinediphosphate (ADP) as well as platelet adhesiveness to collagen of platelet-rich-plasma (PRP) from aspirin-treated patients were explored. ETYA or NDGA (10(-8) and 10(-7) M) clearly diminished the per cent aggregation evoked by collagen or ADP and delayed its onset. On the other hand AA (0.2 mM) enhanced the aggregation and shortened the lag phase evoked by collagen at 1.2 and 2.6 micrograms/ml, but not at 5.2 micrograms/ml. Platelet-collagen adhesion of PRP was significantly reduced by ETYA or NDGA (10(-7) M) and augmented by AA (2 mM). The results strongly suggest that lipoxygenase products of arachidonate metabolism play an important role in promoting the mechanism(s) underlying human platelet aggregation and adhesiveness.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1983

Relationships between prostaglandins and estrogens on the motility of isolated rings from the rat urinary bladder.

We studied the spontaneous contractile activity and the effect of inhibitors of prostaglandin synthesis on the motility of the detrusor muscle isolated from estrous and ovariectomized rats. The constancy with time of the isometric developed tension and of the frequency of contractions of preparations obtained from estrous and spayed rats were not significantly different. In addition, the basal tone was in both cases stable and comparable during the whole experiment. Indomethacin (10(-5) M) or mefenamic acid (10(-5) M) abolished the phasic spontaneous motility whereas the basal tone was significantly diminished with time, the decrement being stabilized after 30 or 40 minutes. The action of inhibitors of prostaglandin synthesis was similar in isolated rings from estrous or ovariectomized animals. Cumulative dose-response curves of PGE2, PGE1 and PGF2 alpha demonstrated that PGF2 alpha evoked contractions with less efficacy and potency than PGs of the E series in both experimental groups. The most important finding was that the dose-response curves of PGE2 and PGE1 were shifted to the right in preparations obtained from ovariectomized rats, whereas the reactivity to PGF2 alpha was similar in estrus or after ovariectomy. In spayed rats injected with 17-beta-estradiol the contractile response of the isolated detrusor to PGE1 had greater efficacy and potency than in preparations from untreated ovariectomized animals. The present findings suggest the possibility that micturition problems commonly found in menopause could be due to a diminished sensitivity to PGE associated to low estrogen levels.

Animals↗
PubMed1983

Contractile activity of the isolated rat vas deferens and release of prostaglandin E and F-like substances. Influences of acetylcholine and inhibitors of cyclo-oxygenase and phospholipase A2.

The isolated epididymal portion of the rat vas deferens releases spontaneously and in response to acetylcholine prostaglandin-like material into the suspending solution. The output of prostaglandin E2 and F2 alpha-like substances, evoked by the cholinergic agonist, was significantly higher than the basal generation. Atropine, but not hexamethonium, markedly reduced the release elicited by acetylcholine. In addition corticosterone, quinacrine and verapamil also decreased significantly the acetylcholine-induced prostaglandin output. Inasmuch as quinacrine and corticosterone antagonized the response to acetylcholine the possible involvement of the cholinergic agonist on the activity of phospholipase A2, is suggested. Furthermore, the role of prostaglandins in relation to the action of acetylcholine on the contractile activity of the epididymal portion of isolated vas deferens, was also explored. It is concluded that these autacoids modulate the contractions evoked by acetylcholine.

Acetylcholine↗