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L Zilletti

Publications and source records attributed to L Zilletti.

At least 19 recordsLinked to original sources
PubMed1992

GABAB receptor-mediated mechanisms in human intestine in vitro.

The spontaneous motility of longitudinal muscle of human jejunum was recorded and the effect of gamma-aminobutyric acid-ergic (GABAergic) drugs was tested. GABA and (-)-baclofen (10(-6)-10(-4) M) dose dependently reduced the amplitude and frequency of the spontaneous contractions; muscimol and 3-aminopropanesulfonic acid (3 x 10(-5) M) were ineffective. The effect of 3 x 10(-5) M GABA was reduced by 3 x 10(-3) M 5-aminovaleric acid but not by 3 x 10(-5) M picrotoxin. The dose-response curve for GABA was shifted to the right by 3 x 10(-3) M 3-aminopropanesulfonic acid. Tetrodotoxin 3 x 10(-7) M prevented the GABAergic action, whereas various receptor antagonists tested did not affect it. GABAergic drugs did not influence the spontaneous motility of either circular or longitudinal muscles of human colon. It is suggested that GABAB receptor activation induces the inhibition of human jejunum longitudinal muscle motility by a neurogenic mechanism. The possible involvement of postganglionic cholinergic neurons is to be evaluated by other techniques.

Colon↗
PubMed1992

D-penicillamine affects lipid peroxidation and iron content in the rat brain cortex.

D-Penicillamine, a trifunctional amino acid known for its ability to form metal complexes and for being a radical scavenger, has been investigated "in vitro" and "in vivo" in the rat brain cortex. At 50 microM the drug facilitated lipid hydroperoxides and TBARS formation in brain cortex homogenates, while at higher concentrations a clear inhibition of the lipid peroxidative process was observed. The activity of the D-penicillamine (25 and 50 mg/Kg i.p.) was evaluated "in vivo" after a 7-day treatment in rats in whose brain cortex a slow process of lipid peroxidation was induced by iron-saccharate injection. Lipid hydroperoxides, lipid soluble fluorescent compounds and the iron content of both iron-injected and contralateral hemicortices showed a significant decrease in comparison to rats untreated with D-penicillamine. The higher dose also induced in normal rats a significant decrease in basal TBARS and iron content of the brain cortex. In the iron-injected cortex the observed Fe2+/Fe3+ ratio was significantly different from that of normal rats. On the contrary ratios obtained form D-penicillamine treated animals were higher in comparison to both normal and iron-injected animals. These results suggest that D-penicillamine, acting as a reducing agent, inhibits the iron redox system and, as a chelating agent, can remove metal from action sites where lipid peroxidation may occur.

Animals↗
PubMed1991

Lipid peroxidation induced "in vivo" by iron-carbohydrate complex in the rat brain cortex.

In view of the emerging role of metals and particularly iron in the pathogenesis of several ischemic or degenerative CNS diseases, via a lipid peroxidative process, a model of slow iron-induced peroxidative damage in the rat brain cortex has been carried out. Iron-carbohydrate complexes were injected in the right brain cortex, and biochemical assays were performed on ipsilateral and contralateral samples two hours or seven days after injection. Iron-saccharate caused a significant increase in the ipsilateral cortex in TBARS, conjugated dienes and fluorescent substances seven days after injection, whereas no biochemical alteration was observed two hours after treatment. In order to prevent or to limit lipid peroxidation, some drugs known for chelating and/or scavenging activity were administered to iron-injected rats. DL-alpha-tocopherol, methylprednisolone, D-penicillamine significantly decreased the value of fluorescent products formed by iron-saccharate, whereas desferrioxamine was not effective.

Animals↗
PubMed1990

Capsaicin and anaphylactic reactions in the guinea-pig airways.

Further evidence is reported on the influence exerted by capsaicin on the anaphylactic reaction evoked in actively sensitized guinea-pigs. In Herxheimer microshock induced by ovalbumin aerosol, pretreatment of animals with 100 micrograms/kg i.p. capsaicin prolonged the preconvulsion time when the drug was administered 3 h before antigen challenge. In contrast, the same dose of capsaicin injected 30 min before aerosol caused a shortening of latency of the respiratory symptomatology. The influence of the drug is no longer evident after 24 h. In "in vitro" experiments desensitization to capsaicin of tracheal preparations caused a reduction of histamine and SRS-A released during antigen challenge, in comparison to controls. Moreover, anaphylactic histamine release was increased in preparations perfused with 10(-8) M substance P. In conclusion, our findings confirm that neuropeptides may be involved in the pathogenesis of asthma by affecting release of mediators.

Anaphylaxis↗
PubMed1990

Glycine-related amino acids stereoselectively affect N-methyl-D-aspartate receptor-mediated contractions of guinea pig ileum: comparison with the inhibition of strychnine-insensitive [3H]glycine binding to rat cortical membranes.

Ten microM glycine, D-serine and D-alanine potentiated L-glutamate (30 microM)-induced contractions of the guinea pig ileum by an average of 35, 53 and 24%, respectively. On the contrary, D-cysteine, at the same concentration, caused a 21% inhibition of the contractile response to L-glutamate. This inhibitory effect of D-cysteine was abolished by 10 microM glycine. The corresponding L-isomers of these amino acids, namely L-serine, L-alanine and L-cysteine and the other amino acids tested, possessed negligible activity or were inactive in this test. The IC50 values of the same compounds for strychnine-insensitive binding of [3H]glycine (20 nM) to cortical membranes from the brain of the rat were: 0.26 microM, glycine; 1.2 microM, D-serine; 2.1 microM, D-alanine; 8.6 microM, D-cysteine; 51 microM, L-serine; 90 microM, L-alanine; greater than 1000 microM, L-cysteine. On the whole, these results point out a strict requirement for stereoselectivity for both of the effects examined. In addition, the results obtained in the ileum preparation suggest that D-cysteine may act as an antagonist, rather than as an agonist at the glycine site which regulates the responses of N-methyl-D-aspartate receptors.

Amino Acids↗
PubMed1989

Peroxidase catalysed formation of prostaglandins from arachidonic acid.

Horseradish peroxidase and bovine lactoperoxidase (EC 1.11.1.7), when incubated aerobically with arachidonate, gave rise to the formation of substances identified by bioassay as prostaglandin F2 alpha (PGF2 alpha)- and prostaglandin E2 (PGE2)-like compounds. Boiling of enzymes, which suppressed their capacity to peroxidize guaiacol, also destroyed their capacity to convert arachidonate into PG-like compounds. The rates of formation of PG-like compounds rapidly declined with time, approaching zero after 10 and 20 min for PGE2 alpha- and PGE2-like compounds, respectively. Addition of more enzyme further promoted the reaction. Horseradish and lacto-peroxidases showed optimum pH values of 9.0 and 10.0, respectively. Both enzymes exhibited apparent Km values of about 5 x 10(-5) M for arachidonate. Some reducing agents such as ascorbic acid, NADH and adrenaline dose-dependently inhibited this reaction. The haem poison, phenylhydrazine, also inhibited, with an IC50 of 1 x 10(-7) M. Indomethacin inhibited only the formation of PGE2-like compounds with an IC50 of about 3 x 10(-6) M. As compared to a standard commercial preparation of horseradish peroxidase, the purified horseradish basic and acidic isoenzymes exhibited a higher activity, towards arachidonate whereas other haemoproteins, possessing peroxidase activity, were less active. TLC and GC-MS analyses performed on the reaction products led to the identification of PGF2 alpha, PGE2 and PG6K1 alpha and other unidentified arachidonate derivatives. At 25 degrees, pH 9.5, horseradish peroxidase, acting on saturating concentration of arachidonate, catalysed the formation of 60 mumol/min/mmole enzyme of PGE2 + PGF2 alpha. This appears to be the first report of the synthesis of prostaglandins catalysed by peroxidases.

Arachidonic Acid↗
PubMed1989

Capsaicin and anaphylactic reactions in the guinea-pig.

The influence of capsaicin on anaphylactic reactions in the guinea-pig was studied both in vivo and in vitro. In guinea-pigs actively sensitized with ovalbumin, Herxheimer microshock was elicited by antigen aerosol and the preconvulsion time recorded. The preconvulsion time was reduced by about 30% in animals pretreated with capsaicin (1 mg/kg) injected i.p. 30 min before antigen aerosol, whereas it remained unchanged when the drug was administered two days before aerosol treatment. Capsaicin shows a partial protective effect when the provocative aerosol was administered 3 h after the last of three doses of capsaicin (100 micrograms/kg, i.p.), which had been injected for three consecutive days. Ileum longitudinal muscle strips were used for in vitro anaphylaxis studies. These were isolated from guinea-pigs actively sensitized with ovalbumin and histamine release evoked by antigen was measured. Preparations perfused with capsaicin (10(-6)-10(-4) M) and desensitized to the drug, showed a lower anaphylactic release of histamine. This effect was dose-dependent, with the histamine release reduced by 35% at higher concentrations (10(-5)-10(-4) M) of capsaicin. The mechanism of the influence of capsaicin on anaphylactic reactions is discussed briefly.

Anaphylaxis↗
PubMed1988

Decreased response to GABA-B agonists in longitudinal smooth muscle-myenteric plexus preparations from morphine-tolerant guinea-pigs.

1) Responsiveness of guinea-pig ileal longitudinal smooth muscle-myenteric plexus preparations to drugs activating GABA-B receptors was studied in morphine-tolerant animals. For this purpose morphine pellets (75 mg each) were implanted subcutaneously in guinea-pigs and experiments were performed three days later in electrically-stimulated ileal strips. 2) Activation of GABA-B receptors with GABA (10(-6) -10(-3) M) or (-)-baclofen (10(-6)-10(-3) M) caused a dose-related inhibition of twitch response that was about 80% lower in preparations from morphine-tolerant animals than in controls. This was found both in preparations maintained in the presence of morphine (10(-6) M) and in morphine-free Krebs. The effect was evident also in ileal preparations from morphine-tolerant animals in which a withdrawal syndrome was induced by the administration of naloxone before sacrifice. 3) The phenomenon was specific since the dose-response curve of the adenosine-inhibitory effect was comparable in preparations from tolerant animals and controls. 4) The hyporesponsiveness to GABA-B receptor activation began 12 h after pellet implantation and was maximal on the third day. 5) It is concluded that during tolerance to and withdrawal from morphine there is a hyporesponsiveness of GABA-B receptors in "in vitro" guinea-pig ileal longitudinal muscle-myenteric plexus preparations.

Animals↗
PubMed1988

Agonists, antagonists and modulators of excitatory amino acid receptors in the guinea-pig myenteric plexus.

1. The receptors for glutamic acid (L-Glu) present in the guinea-pig myenteric plexus-ileal longitudinal muscle preparation have been studied by measuring the muscle contraction induced by numerous putative endogenous agonists acting at these receptors. Furthermore, the actions of different concentrations of antagonists, glycine, Mg2+ and Ca2+ on the ileal contractions induced by L-Glu have been evaluated. 2. The EC50 values of the most common putative endogenous agonists of these receptors were: L-Glu 1.9 X 10(-5) M; L-aspartate 8 X 10(-5) M; quinolinate 5 X 10(-4) M; L-homocysteate 1.4 X 10(-4) M; the dipeptide aspartyl-glutamate 8 X 10(-5) M, while N-acetyl-aspartyl-glutamate was inactive. Among the molecules used to classify excitatory amino acid receptors, N-methyl-D-aspartate (NMDA) was the most potent (EC50 5 X 10(-4) M). Kainic and quisqualic acids were almost completely inactive. 3. The responses to L-Glu were competitively antagonized by 2-amino-5-phosphonovaleric acid. They were, also, prevented by hyoscine (10(-7) M) and by tetrodotoxin (3 X 10(-7) M), suggesting that the L-Glu-induced ileal contraction was in some way dependent upon an action on the myenteric cholinergic neurones. Kynurenic acid was a non-competitive antagonist, gamma-D-glutamyl-taurine (10(-4) M) and aminophosphonobutyric acid (10(-4) M) did not modify the L-Glu-induced contractions. 4. Glycine (10(-5) M) significantly potentiated the effects of glutamate especially when the ionic composition of the superfusion medium contained concentrations of Ca2+ in the range of 0.6-1.2 mM. Strychnine 3 X 10(-5) M did not modify the actions of glycine. 5. The data presented here confirm the presence of NMDA receptors in the guinea-pig myenteric plexus, and show that these receptors, similar to those present in primary neuronal cultures may be modulated by glycine.

Animals↗
PubMed1987

Effect of various GABA-receptor agonists and antagonists on anaphylactic histamine release in the guinea-pig ileum.

In this paper we confirm the previously reported inhibition by GABA of anaphylactic histamine release from isolated guinea-pig ileum longitudinal muscle. Moreover we report that: GABA-inhibition of anaphylactic histamine release is mimicked both by GABA-A and GABA-B agonists; both GABA-A and GABA-B antagonists are effective in reversing GABA's inhibitory effect; the effect is exerted specifically by GABA-ergic drugs: taurine and beta-alanine are ineffective; the GABA-ergic effect seems not to involve cholinergic and adrenergic transmission. It is concluded that it might be interesting to assess the clinical value of GABA-ergic drugs in allergic gut disorders.

Anaphylaxis↗
PubMed1987

Effect of baclofen on different models of bronchial hyperreactivity in the guinea-pig.

In this paper we report an inhibitory effect of (-)-baclofen on many models of bronchial hyperreactivity both in vivo and in vitro. (-)-Baclofen protects guinea-pigs from the anaphylactic bronchospasm induced in sensitized animals by an ovalbumin aerosol and from that induced by aerosols of histamine and PGF2 alpha. Moreover (-)-baclofen reduces the TXA2 and TXB2 output induced by ovalbumin from isolated sensitized guinea-pig lungs. On the other hand (-)-baclofen does not show antihistaminic, anticholinergic or antiprostaglandinic action on isolated tracheal preparations. It is concluded that baclofen can provide protection from bronchial hyperreactivity possibly through a modulation of autonomic nervous system activity.

Acetylcholine↗
PubMed1987

Effects of nesosteine on Herxheimer microshock in guinea-pigs.

In this paper we firstly report the inhibitory effect of nesosteine, a mucolytic drug, on Herxheimer microshock in guinea-pigs. Nesosteine (5-50 mg/kg) is able to protect sensitized animals from ovalbumin-induced bronchospasm. On the other hand, the drug is ineffective against the bronchospasm induced by histamine and acetylcholine. These results have also been confirmed in in vitro experiments where it has been demonstrated that nesosteine (10(-5) M) inhibits ovalbumin-induced histamine release in the trachea of sensitized animals. In the same preparation, the drug is ineffective against the contractions induced by histamine or acetylcholine. In conclusion, the drug presented here may be helpful in pathological conditions where reductions both of mucolysis and bronchospasm are sought.

Anaphylaxis↗
PubMed1987

Rhein: an anthraquinone that modulates superoxide anion production from human neutrophils.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the active metabolite of diacetylrhein, which has been reported as an effective antirheumatic drug in man, inhibited superoxide anion production from human neutrophils challenged with N-formylmethionyl-leucyl-phenylalanine (FMLP: IC50, 2 x 10(-5) M) and A23186 (IC50, 10(-5) M), but not with phorbol myristate acetate. In the same concentration range (10(-6)-10(-3) M), the drug did not affect oxy-radical production by a cell-free hypoxanthine-xanthine oxidase system and exerted weak inhibitory effects on FMLP-evoked lysosomal enzyme release. Rhein inhibitory effects on neutrophil functioning may contribute to the overall therapeutic activity of the parent drug, diacetylrhein.

Adult↗
PubMed1986

The presence of N-methyl-D-aspartate-type receptors for glutamic acid in the guinea pig myenteric plexus.

The actions of agonists and antagonists of excitatory amino acid receptors were studied in the isolated ileal longitudinal muscle-myenteric plexus preparation of the guinea pig incubated 'in vitro', by recording the contraction of the longitudinal muscle. L-Glutamate, L-aspartate, quinolinate and N-methyl-D-aspartate (NMDA), in concentrations ranging from 10(-6) to 10(-4) M, induced a rapid contraction of this preparation while kainate and quisqualate were not active at a concentration of 10(-4) M. The excitatory amino acid responses were competitively antagonized by 2-amino-5-phosphonovalerate. They were also prevented by Mg2+ ions (0.1-1 mM), by tetrodotoxin 3 X 10(-6) M and by hyoscine 10(-7) M. The last observations suggest that the myenteric cholinergic interneurons are in some way involved in the glutamate-induced ileal contraction. These results demonstrate the existence of receptors for excitatory amino acids (possibly of NMDA type) in the myenteric plexus of the guinea pig.

Animals↗
PubMed1986

The effect of lipoxygenase inhibitors and leukotriene antagonists on anaphylaxis.

The experiments whose results are reported here were carried out with the aim of showing a possible role for lipoxygenase products in the modulation of the Schultz-Dale reaction. For this purpose, the actions of nordihydroguaieretic acid (NDGA) and of FPL 55712 were tested during anaphylaxis in guinea-pig ileum and trachea in vitro. Isolated preparations from guinea-pigs, which had been subcutaneously sensitized with ovalbumin and incomplete Freund adjuvant, were challenged with increasing concentrations of antigen; in preparations isolated from the same animal an antigen-concentration anaphylactic-reaction curve was performed in the presence of the drugs. NDGA 3.3 X 10(-6) M was capable of inhibiting anaphylaxis in the trachea to a maximum extent of 40% but it did not affect anaphylactic reaction in the intestinal smooth muscle. FPL 55712 2 X 10(-6) M did not exert any activity on anaphylaxis in either preparations. The difference between SRS-A and histamine as mediators of anaphylaxis in the tissue preparations used could explain the fact that NDGA acted on the trachea alone.

Anaphylaxis↗