PubMed Health⌕ Search

Biomedical subjects

L Manzo

Publications and source records attributed to L Manzo.

At least 73 records · Page 4Linked to original sources
PubMed1991

Two subtypes of enteric non-opioid sigma receptors in guinea-pig cholinergic motor neurons.

In the longitudinal muscle-myenteric plexus preparation (LMMP) of the guinea-pig ileum, the non-opioid sigma receptors agonists, 1,3-di-ortho-tolylguanidine (DTG) and (+)N-allyl-N-normetazocine [(+)SKF 10,047], had opposite effects on nerve-mediated cholinergic contractions caused by electrical field stimulation. DTG (0.1-10 microM) inhibited and (+)SKF 10,047 (0.1-10 microM) markedly enhanced these contractile responses. Both effects were evaluated in the presence (0.5 or 1 microM) of the putative antagonists at central sigma sites: haloperidol, rimcazole, BMY 14802 and dextromethorphan. Haloperidol and dextromethorphan were ineffective. Rimcazole antagonized the effect of both DTG and (+)SKF 10.047. BMY 14802 antagonized the (+)SKF 10.047-mediated excitatory response only. These results suggest that two sigma receptor subtypes are present in enteric cholinergic motor neurons innervating the longitudinal coat. Rimcazole and BMY 14802 may provide useful tools for the characterization of peripheral non-opioid sigma receptors.

Animals↗
PubMed1991

Time-, concentration-, and age-dependent inhibition of muscarinic receptor-stimulated phosphoinositide metabolism by ethanol in the developing rat brain.

We have previously reported that administration of ethanol (EtOH; 4 g/Kg/day) to rats from postnatal day 4 to day 10 causes microencephaly and decreases muscarinic receptor-stimulated inositol metabolism on days 7 and 10. An identical exposure to EtOH of adult rats, which resulted in similar blood EtOH concentrations, did not have any effect on the same system. Initial in vitro studies have shown the presence of a differential sensitivity to EtOH of the phosphoinositide system coupled to muscarinic receptors during development. In the present study we have expanded these findings by investigating the concentration-, time-, and age-dependent effects of EtOH on accumulation of [3H]inositol phosphates ([3H]InsPs) in brain slices. EtOH caused a dose-dependent inhibition of carbachol-stimulated phosphoinositide metabolism in cerebral cortex slices from 7 day-old rats. When the time of incubation with EtOH was increased to 90 minutes, concentrations as low as 50 mM, which are reached following in vivo administration of EtOH, significantly inhibited the muscarinic response. The effect of EtOH was rather specific for the muscarinic receptors, since, even with longer incubation times, the accumulation of [3H]InsPs induced by norepinephrine or serotonin was inhibited only at concentrations of 150-500 mM. The effect of EtOH was more pronounced in cerebral cortex, hippocampus and cerebellum, and less in the brainstem. The potency of EtOH in inhibiting carbachol-stimulated phosphoinositide metabolism was also dependent on the age of the animals. Its effect was maximal in the 7-day-old rat and less pronounced in younger and older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Biliary excretion of barium in the rat.

Biliary excretion of barium was studied in Sprague-Dawley bile-duct-cannulated rats injected intravenously with 1.8 micrograms Ba/rat as 133Ba-labeled barium chloride. Approximately 0.5% of the barium dose was excreted into bile within 2 h. The time-course profile of biliary excretion of the radiotracer closely reflected that of plasma concentrations. Biliary barium levels reached their peak in the first 15-min period after administration and rapidly declined thereafter. The plasma-to-bile barium-concentration ratio was approx 1 at 2 h after injection. There was no tendency of barium to concentrate in liver, and the 133Ba levels in stomach and small intestine largely exceeded hepatic levels. There is evidence indicating that barium is predominantly excreted with feces following parenteral administration in rats and humans. The results of this study suggest that biliary excretion is of little quantitative importance and that physiological routes other than bile contribute to elimination of barium by the digestive tract.

Animals↗
PubMed1991

Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes.

Aluminum (Al) is believed to exert a primary role in the neurotoxicity associated with dialysis encephalopathy and has been suggested to be involved in a number of other neurological disorders, including Alzheimer's disease. Al, complexed with fluoride to form fluoroaluminate (AlF4-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study we investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated [3H]inositol phosphates ([3H]InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, which is known to exert a negative feedback control on agonist-stimulated PtdIns metabolism. Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic, suggesting that AlF4- could be the active stimulatory species. However, the stimulatory effects of AlCl3 and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA, suggesting that separate sites of action might exist for GTP(S) and AlF4-. In the nervous tissue, activation of PtdIns hydrolysis by Al (probably as AlF4-) may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C.

Aluminum↗
PubMed1991

Modifications of cell signalling in the cytotoxicity of metals.

Many metals act on biological systems at low concentrations and recent epidemiological and experimental research indicates that toxic effects of certain metals occur at levels only marginally higher than those found in healthy subjects. Despite a large number of studies describing metal cytotoxicity, the molecular mechanisms involved are still poorly understood. However, it now seems evident that several metals can interact with enzyme functional groups and that proteins involved in signal transduction, including Ca2+ channels and pumps, may be especially sensitive to this interaction. Impairment of the ability of cells to adequately respond to the stimulation by hormones and growth factors may result in the loss of important cell functions or activation of mechanisms that compromise cell survival. In the following sections we will briefly describe the effects of various metals on cell signalling and present our recent findings on the mechanism by which inorganic mercury affects signal transduction.

Animals↗
PubMed1991

Muscarinic M2 receptors in rat brain labeled with [3H] AF-DX 384.

The muscarinic antagonist AF-DX 384 (5,11-dihydro-11-(((2-(2-((dipropylamino)methyl)-1- piperidinyl)ethyl)amino)carbonyl)-6H-pyrido(2,3b)(1,4)-benzodiazepin+ ++-6-one methansulfonate) was used to label cholinergic muscarinic receptors of the M2 subtype in rat brain. In the brainstem [3H] AF-DX 384 labeled a single population of binding sites with Kd = 3-4 nM and Bmax = 430-610 fmol/mg of protein. The pharmacological profile of these sites was similar to that observed with the muscarinic M2 agonist [3H] AF-DX 116. Muscarinic M2 receptors were unequally distributed in rat brain regions: in brainstem, about 80% of total muscarinic receptors (measured with [3H] quinuclidinyl benzilate) were labeled by [3H] AF-DX 384, while in other brain areas they represented only a fraction of total binding. Because of its high specific binding, high affinity and specificity, [3H] AF-DX 384 represents a useful novel ligand to study M2 receptors in brain tissue.

Animals↗
PubMed1990

Tributyltin stimulates apoptosis in rat thymocytes.

Treatment of rat thymocytes with micromolar concentrations of tributyltin caused a rapid increase in the cytosolic free Ca2+ concentration that was inhibited by Ni2+, which blocks Ca2+ influx through membrane channels. The elevation of cytosolic Ca2+ was associated with extensive DNA fragmentation, which was prevented by pretreatment of the cells with either of the intracellular Ca2+ chelators quin-2 or 1,2-bis(2-amino-phenoxy)ethane-N',N',N',N',-tetraacetic acid. Loss of thymocyte viability, which followed DNA fragmentation, was also prevented by the two Ca2+ chelators or by removing extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid. The pattern of DNA fragmentation was characteristic of that produced by agents which activate a Ca2(+)- and Mg2(+)-dependent endogenous endonuclease during apoptosis or programmed cell death. Additional studies showed that other organotin compounds, including trimethyltin, triphenyltin, and dibutyltin had minimal effects on cytosolic Ca2+, DNA fragmentation, and cell viability. These results are consistent with a greater susceptibility of thymocytes to tributyltin and provide a basis for understanding its selective immunotoxicity in vivo.

Animals↗
PubMed1990

1,2-Dichloropropane hepatotoxicity in rats after inhalation exposure.

The hepatic effects of 1,2-dichloropropane (DCP) were investigated in male Wistar rats exposed to 15, 50, 100, 250, 450, 1000, 1300, 1800 or 4900 mg DCP m-3. At the end of a 4-h period of exposure, average blood DCP levels were 0.025 and 5.38 micrograms ml-1 in animals treated with 15 and 1300 mg m-3, respectively. Blood DCP concentrations were correlated with the air DCP concentrations in the inhalation chamber. At DCP concentrations of 100 mg m-3 or higher, the liver non-protein thiol (NPT) content was significantly reduced. Assays performed 20 h after 4-h DCP exposure showed that exposure to 100-1000 mg DCP m-3 had no effect on hepatic NPT levels. The NPT content increased only in the liver of rats exposed to higher (1300-4900 mg m-3) DCP concentrations. Treatment with DCP did not cause hepatic lipid peroxidation and did not modify total protein content. The observed changes in liver cell thiol homeostasis are likely to reflect the action of reactive intermediates formed during DCP metabolism. These changes can occur in rats following exposure to considerably low levels of DCP vapour.

Administration, Inhalation↗
PubMed1990

Interaction of sigma-compounds with receptor-stimulated phosphoinositide metabolism in the rat brain.

Sigma-receptors are nonopioid, nondopaminergic receptors that bind with high affinity several antipsychotic drugs and appear to be involved in regulation of posture and movement. The second messenger system coupled to these receptors is still unknown. Recently, an inhibitory effect of various sigma-compounds on carbachol-stimulated phosphoinositide metabolism has been reported. We have investigated the effect of six sigma-compounds on carbachol- and norepinephrine-stimulated 3H-inositol phosphate accumulation in rat cerebral cortex slices. All compounds tested had a dose-dependent inhibitory effect on both systems, although their order of potency differed between neurotransmitters. Pentazocine and 1,3-di-o-tolylguanidine were the most potent inhibitors of carbachol-stimulated phosphoinositide turnover (IC50 = 31.5 and 45.7 microM, respectively), while haloperidol showed the greatest potency on the norepinephrine-coupled system (IC50 = 3.5 microM). In the presence of IC50 concentrations of these inhibitors, the dose-response curves for the agonists were shifted to the right and the EC50 values were significantly increased. Sigma-compounds also inhibited the binding of [3H]quinuclidinyl benzilate to muscarinic receptors and of [3H]prazosin to alpha 1-adrenoceptors in cortical membranes. In the presence of IC50 concentration (11 microM) of 1,3-di-o-tolylguanidine, no differences were found in the maximal number of muscarinic binding sites, whereas the dissociation constant increased approximately fivefold, indicating a decrease of the radioligand's affinity for the receptor. These results indicate that sigma-compounds, at micromolar concentrations, inhibit muscarinic and alpha 1-adrenergic receptor-coupled phosphoinositide metabolism, probably through an interaction with the neurotransmitter recognition sites.

Animals↗
PubMed1989

The role of GABAA receptor function in peristaltic activity of the guinea-pig ileum: a comparative study with bicuculline, SR 95531 and picrotoxinin.

1. The peristaltic activity of the guinea-pig ileum was studied in the absence and in the presence of the blockade of GABAA receptors. 2. Bicuculline (1-30 microM), improved at the highest concentrations the efficiency of peristalsis by enhancing the frequency of propulsive contractions and the amount of fluid ejected per unit of time. 3. Neither SR 95531 (0.3-10 microM), a novel GABAA receptor antagonist, which competitively antagonized 3-aminopropane sulphonic acid induced contractions in myenteric plexus-longitudinal muscle preparations (pA2 value: 6.47), nor picrotoxinin (1-30 microM) modified peristaltic parameters or influenced the potentiating effect of bicuculline on peristaltic activity. 4. In myenteric plexus-longitudinal muscle preparations, bicuculline (1-30 microM) enhanced the amplitude of electrically-induced cholinergic contractions without modifying submaximal contractions to applied acetylcholine. SR 95531 and picrotoxinin had no effect on twitch amplitude. In the presence of each of these compounds, bicuculline retained its potentiating effect. 5. The results obtained with SR 95531 and picrotoxinin question the view that GABAA receptors may exert a critical role in intestinal propulsion by modulating the activity of nerve pathways subserving peristalsis. Bicuculline potentiates the peristaltic activity of the ileum probably via a facilitatory effect on enteric cholinergic transmission that is independent of GABAA receptor blockade.

Animals↗
PubMed1989

An in vitro study of the relationship between GABA receptor function and propulsive motility in the distal colon of the rabbit.

1. The effects of gamma-aminobutyric acid (GABA), 3-aminopropane sulphonic acid (3-APS) and baclofen on spontaneous, electrically-induced and propulsive motility were investigated in rabbit distal colon. 2. In unstimulated longitudinal (LMPs) and circular muscle strip preparations (CMPs) 3-APS (10-200 microM) and GABA caused a clear-cut relaxation susceptible to desensitization. Baclofen (10-200 microM) caused relaxation in a minority (30%) of preparations. The 3-APS response was sensitive to tetrodotoxin (TTX; 1 microM), SR 95531 (a novel competitive GABAA-receptor antagonist) (10 microM), picrotoxinin (30 microM), and insensitive to hyoscine (1 microM) and to a combination of prazosin (1 microM) and propranolol (1 microM). The baclofen response was antagonized by 5-aminovaleric acid (DAVA, 500 microM), TTX and hyoscine and resistant to GABAA-receptor and adrenoceptor blockade. GABAA-receptors were therefore associated with non-adrenergic non-cholinergic (NANC) inhibitory nerve activation while GABAB-receptors were involved in depression of cholinergic tone of smooth muscle. GABA (10-200 microM) elicited both above mentioned effects. 3. In LMPs, baclofen (10-200 microM) dose-dependently inhibited submaximal responses to both cholinergic and NANC inhibitory nerve stimulation. This effect was resistant to SR 95531 and picrotoxinin and prevented by DAVA and baclofen desensitization. GABA (10-200 microM) mimicked the action of baclofen. GABA inhibitory effects persisted in the presence of GABAA-receptor blockade. 4. In segments of distal colon, GABA and baclofen (1-200 microM), but not 3-APS (1-200 microM), dose-dependently decreased the velocity of propulsion of an intraluminally-distended balloon. This effect was antagonized by DAVA and GABA or baclofen desensitization and resistant to SR 95531 and picrotoxinin. These antagonists per se had no effect on propulsion. In preparations in which propulsion was slowed by hyoscine (1 microM), baclofen caused no consistent further depression of propulsive activity. 5. Our results show that GABAA- and GABAB-receptors are present in rabbit colon. GABAA-receptor stimulation activates NANC inhibitory nerves without apparently affecting propulsion. GABAB-receptors are associated with a reduction of neural (mainly cholinergic) activity subserving muscular tone and peristalsis and appear to be located on both cholinergic and NANC inhibitory nerves. However, the persisting propulsive activity during suppression of GABAA- and GABAB-receptor function suggests that GABA in enteric neurones is not crucial for the neural circuitry subserving colonic peristalsis in this species.

Amino Acids↗
PubMed1989

Effect of beta-casomorphins on intestinal propulsion in the guinea-pig colon.

beta-Casomorphins are a family of opioid peptides originally isolated from beta-casein. In view of a possible physiological significance of these milk-derived compounds, the effects of bovine beta-casomorphin-5 (beta-CM-5), beta-casomorphin-4 (beta-CM-4) and D-Ala2-beta-casomorphin-4-NH2 (D-Ala2-beta-CM-4-NH2) have been investigated on the peristaltic reflex in the guinea-pig isolated colon and compared with morphine. beta-CM-5 and D-Ala2-beta-CM-4-NH2 each dose-dependently inhibited the velocity of propulsion of an intraluminal bolus; beta-CM-4 was ineffective. IC50 values were 0.30, 5.21 and 0.29 microM for morphine, beta-CM-5 and D-Ala2-beta-CM-4-NH2, respectively. The potency ratios vs morphine were 0.06 and 0.96 for beta-CM-5 and D-Ala2-beta-CM-4-NH2, respectively. Blockade of the peristaltic reflex by beta-CM-5 or D-Ala2-beta-CM-4-NH2 was reversed by the opioid antagonist naloxone. D-Ala2-beta-CM-4-NH2 also dose-dependently inhibited resting acetylcholine output (IC50 = 5.69 microM; potency ratio vs morphine: 0.63). In conclusion, certain beta-casomorphins inhibit intestinal propulsion and cholinergic neurotransmission in the guinea-pig colon, probably by acting at opioid receptors.

Acetylcholine↗
PubMed1989

Interaction of the pyrethroid insecticides tetramethrin and cypermethrin with enteric cholinergic transmission in the guinea-pig.

In electrically-stimulated longitudinal muscle-myenteric plexus preparations of the guinea-pig ileum, the Type I pyrethroid insecticide tetramethrin (1-100 microM) caused a biphasic response consisting of an early transient increase followed by a sustained decrease in the amplitude of cholinergic contractions. The cholinergic potentiation was antagonized by phenytoin (3 microM), which also prevented the increase in twitch height caused by veratridine (30 nM). The late inhibitory effect of tetramethrin probably involved a direct action on the musculature since contractile responses to applied acetylcholine (100 nM) or histamine (300 nM) were also depressed by this compound. Cypermethrin (1-100 microM), a Type II pyrethroid, had only a minor enhancing effect on electrically evoked contractions. Cypermethrin (30, 60 microM), but not tetramethrin, antagonized the cholinergic response induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (1-100 microM). These results suggest that neural Na+ channels activation may underlie pyrethroid-induced potentiation of enteric cholinergic transmission. In small intestine, however, cypermethrin is also effective as a noncompetitive antagonist of GABA-A receptor mediated cholinergic contractions.

Animals↗
PubMed1988

Effects of silver in isolated rat hepatocytes.

Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 microM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes.

Animals↗
PubMed1987

Involvement of substance P in the excitatory action of GABAA agonists on cholinergic neurons in the guinea-pig ileum.

The possible involvement of substance P (SP) in cholinergic contractions induced by GABAA agonists in the guinea-pig ileum was further investigated. Responses evoked by 3-aminopropane sulphonic acid (3-APS) or muscimol consisted of a rapid phasic contraction followed in 70% of preparations by a tonic contraction, usually smaller in amplitude but considerably longer in duration. Phasic and tonic components were sensitive to bicuculline, neurogenic (cholinergic) in nature and susceptible to desensitization. Capsaicin (0.2 microM) pretreatment and SP receptor desensitization caused by 3 different priming SP concentrations (10 nM, 30 nM, 100 nM), depressed both components of the 3-APS-induced response, the magnitude of antagonism being greater for tonic contractions. Similar findings were obtained by using 10 microM (D-Pro4,D-Trp7.9)SP-(4-11), even though the degree of antagonism caused by this SP antagonist was consistently lower. These results indicate that depression of SP receptor function achieved by three different procedures decreases cholinergic contractile responses to GABAA agonists in the guinea-pig ileum. This provides further support for the hypothesis that GABAA receptor activation evokes both direct and indirect stimulation of enteric cholinergic neurons and that SP and/or a related peptide play an important role in mediating the indirect component of the cholinergic response.

Animals↗
PubMed1987

[Suboccipital Pott's disease].

A new case of sub-occipital Pott's disease is reported: a 26 year old, coloured male patient from Senegal was admitted for: cervical pain of 6 month duration, neck stiffness, dysphagia, left XII paralysis and left hemiparesis. The radiological study found an anterior atlanto-axial subluxation, basilar impression, and increased thickness of the retropharyngeal soft tissue, lysis of the left occipital condyle and the left lateral mass. CT scan study revealed a retropharyngeal mass and an epidural contrast-enhanced lesion at the C2 C3 C4 levels. Chest-X ray showed one tuberculous lesion at the right apex. The research of Acid Fast Bacilli in gastric secretion samples and the results of the retropharyngeal mass puncture were positive. An antituberculous trichemotherapy was started. After early reduction by skull tongs traction, an occipito-cervical arthrodesis by Roy Camille plates was performed, followed by the wearing of a minerva plaster jacket and then a plastic collar. Each one for a 5 month period. One year later, there remained only a left XII paralysis, but the bony reconstruction was not yet obvious on tomography. A survey of the literature of 70 cases of sub-occipital Pott's disease has pointed out these findings: cervical pain (98%), neck stiffness (82%), Atlantoaxial subluxation (68%), thickened prevertebral soft tissue shadow (77%), lateral mass lysis (48%) other tuberculous focus (29%). The main therapeutic trends are: early and long-lasting antituberculous poly-chemotherapy, early reduction of subluxations, prolonged contention for slight osteolytic lesions and for major: lytic lesions, a posterior surgical procedure either by bone graft combined with wires or preferably fusion by means of occipito-cervical plates. The removal of abscess is discussed.

Adult↗
PubMed1986

Triphenyl tin hepatotoxicity in rats.

Hepatic microsomal aniline hydroxylase and aminopyrine N-demethylase in vitro activities and the biliary excretion of sulfobromophthalein (BSP) were significantly reduced in rats treated with triphenyl tin (TPT) in daily doses of 1 mg/kg i.p. for 3 days. Bile flow, liver weight, serum enzyme activities, and hepatic sulfhydryl groups and thiobarbituric reactant levels were unaffected in TPT-treated animals. Moreover, TPT failed to induce any appreciable change in the biliary excretion of both the organic base procainamide ethobromide and the organic acid amaranth which is excreted into the bile in the unmetabolized form. TPT has been shown to be an effective inhibitor of rat liver glutathione-S-transferase activity. Reduced conjugation with glutathione may play a role as a factor determining the low rate of biliary BSP excretion in the TPT-treated rats.

Aminopyrine N-Demethylase↗