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L Beani

Publications and source records attributed to L Beani.

At least 19 recordsLinked to original sources
PubMed1992

Muscarinic modulation of acetylcholine release from slices of guinea pig nucleus basalis magnocellularis.

Spontaneous and electrically evoked endogenous acetylcholine release and [3H]-choline efflux from slices of guinea pig nucleus basalis magnocellularis (nbM) were studied. Tetrodotoxin reduced the spontaneous endogenous release by 55%, while the Ca(2+)-free medium reduced it by about 30%. Evoked [3H]-choline efflux was Na+ and Ca2+ dependent and frequency related. Physostigmine, 30 microM, nearly halved the stimulation-evoked efflux; atropine, 0.15 microM, not only antagonized, but even reversed this effect into facilitation. Pirenzepine, 1 microM, and AFDX 116, 1 microM, were less effective than atropine, and reversed the inhibitory effect of physostigmine only when applied together. 4-DAMP, 0.01 microM, was ineffective. These findings indicate that acetylcholine release in guinea pig nbM slices is inhibited by the cooperation of muscarinic autoreceptors, possibly belonging to the M1 and M2 subclasses.

Acetylcholine↗
PubMed1992

A simple method for electrical field stimulation of cultured granule cells.

A method suitable for electrical field stimulation of superfused primary cultures of cerebellar granule cells is described. A microchamber of about 0.5 ml was obtained by closing the culture dishes with a perspex plug equipped with stimulating electrodes and inlet-outlet tubing. Two-minute trains of electrical pulses (alternate polarity, 2-ms duration; 100 mA intensity; 10 V drop between electrodes; frequency 5, 10 and 20 Hz) applied to cultures kept at 27 degrees C, elicited a D-[3H]aspartate outflow which was frequency related, [Ca2+]0 dependent, tetrodotoxin sensitive. Moreover 2 trains of 10 Hz pulses (S1 and S2) at 30-min intervals caused an S2/S1 ratio equal or near to one, thus demonstrating that a steady-state condition had been achieved. The NMDA antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) but not the non-NMDA antagonist, 6-cyano-7-nitroquinozaline-2,3-dione (CNQX), added before S2, significantly increased the electrically evoked tritium efflux, suggesting that the endogenous transmitter released during electrical stimulation activated an NMDA-mediated negative feed-back. This technique of electrical field stimulation seems particularly feasible to study the extent and time course of drug effects on spontaneous and evoked D-[3H]aspartate outflow.

2-Amino-5-phosphonovalerate↗
PubMed1992

Changes in gamma-aminobutyric acid release induced by topical administration of drugs affecting its metabolism and receptors: studies in freely moving guinea pigs with epidural cups.

The effect of local application of drugs affecting gamma-aminobutyric acid metabolism and receptors on cortical aminoacid release has been investigated in freely-moving guinea pigs equipped with epidural cups. Topical treatment with gamma-aminobutyric acid reuptake and/or metabolism inhibitors (alone and in combination) produced a slow and progressive increase in cortical aminoacid release. The inhibition of gamma-aminobutyric acid-transaminase with ethanolamino-O-sulphate seemed to be a suitable procedure for enhancing the gamma-aminobutyric acid efflux without interfering with its autoreceptor-mediated negative feedback, tested with the gamma-aminobutyric acid agonist (+/-)baclofen and antagonist phaclofen. A substantial part of the gamma-aminobutyric acid outflowing from the cortex was of neuronal origin since tetrodotoxin halved the basal efflux in the presence of gamma-aminobutyric acid reuptake and/or metabolism inhibitors. These results, considered together, indicate that the epidural cup technique may be a useful approach to study changes in cortical gamma-aminobutyric acid release induced by drugs acting on gabaergic transmission and directly applied on the surface of the cortex.

4-Aminobutyrate Transaminase↗
PubMed1992

Clonidine inhibition of norepinephrine release from normal and morphine-tolerant guinea pig cortical slices.

Endogenous norepinephrine (NE) release in cerebral cortex slices taken from normal and morphine-tolerant guinea pigs was measured by HPLC. In normal slices, a linear relationship was found between electrically evoked NE release and the log of the frequency of stimulation in the range of 1-20 Hz. The efficiency of the alpha 2-mediated autofeedback was tested by adding the alpha 2-agonist clonidine and the alpha 2 agonist idazoxan. NE release was dose-dependently reduced by clonidine (1 nmol/L-1 mumol/L) and increased by idazoxan (10-100 nmol/L). The inhibition by clonidine was significantly greater at 1 Hz than at 3 Hz, whereas the absolute increase in NE release induced by idazoxan was greater at 3 Hz than at 1 Hz. Morphine at 1 mumol/L (a concentration per se ineffective) shifted to the left the clonidine concentrations able to inhibit NE release at 3 and 1 Hz (1-10 nmol/L), but at both frequencies, the opiate reduced the maximal inhibition induced by clonidine at 1 mumol/L. In slices taken from morphine-tolerant guinea pigs (in the presence of morphine at 1 mumol/L), clonidine (1 nmol/L-1 mumol/L) was ineffective at the stimulation rate of 3 Hz, but it was more active than in normal slices at 1 Hz. Such a response pattern suggests a reduced availability of alpha 2 receptors and an increase in their sensitivity to clonidine. However, chronic morphine treatment did not influence the physiological autoinhibition because the increase in NE release elicited by idazoxan (10-100 nmol/L) at 1 and 3 Hz was the same in normal and in "morphine-tolerant" slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

Comparison of [3H]choline and D-[3H]aspartate efflux from guinea pig and human neocortex.

The outflow of [3H]choline ([3H]Ch) evoked by electrical field stimulation and the efflux of D-[3H]Asp induced by 35 mM KCl and 1-10 microM ouabain were studied in human and guinea pig cortical slices, kept under identical experimental conditions. [3H]Ch outflow was significantly lower whereas D-[3H]Asp efflux was significantly higher in humans than in guinea pigs. This suggests a different proportion of the two neuronal systems in these two species. Blockade of muscarinic autoreceptors with atropine increased, whereas stimulation of alpha 2 receptors with norepinephrine (NE) reduced, the evoked [3H]Ch outflow to the same extent in human and guinea pig cortical slices. Conversely, NE did not affect ouabain-induced D-[3H]Asp efflux, suggesting that an alpha 2-mediated control is not operative in the glutamatergic cortical structures. Desmethylimipramine, 2-5 microM, was able to increase [3H]Ch outflow through atropine-like mechanisms only in the human. This drug at 20-50 microM inhibited [3H]Ch and D-[3H]Asp efflux in both species, through mechanisms unrelated to its monoamine reuptake blocking properties. Thus, similarities and differences can be detected between humans and guinea pigs with regard to (a) the relative potency of the cholinergic and acidic amino acidergic signals and (b) the modulation of neurotransmitter outflow by drugs acting on auto- and the heteroreceptors.

Animals↗
PubMed1991

Inhibitory effect of NMDA receptor activation on quisqualate-stimulated phosphatidylinositol turnover in the human cerebral cortex.

The effect of excitatory amino acids (EAA) on the phosphatidylinositol (PI) turnover in human cerebral cortical slices was investigated. Quisqualic acid (QA) and, to lesser extent, ibotenic acid (IBO) at 10(-5)-10(-3) M increased inositol phosphate (IP) accumulation. L-Glutamic acid (L-glu), kainic acid (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartic acid (NMDA) were ineffective. NMDA dose-dependently antagonized the QA facilitatory effect. Such inhibition was prevented by the NMDA receptor complex antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine (MK-801) and by 3[+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid. The effect of IBO (but not that of QA) was greatly potentiated by MK-801. These data suggest that the EAA metabotropic receptor described in the rodent brain is also present in human cerebral cortex and is negatively modulated by the NMDA receptor.

Amino Acids↗
PubMed1991

Glutamate antagonists prevent morphine withdrawal in mice and guinea pigs.

The effects of excitatory amino acid antagonists on increased cortical acetylcholine release and behavioral hyperactivity induced by naloxone in morphine tolerant guinea pigs and mice were studied. The results show that the N-methyl-D-aspartic acid (NMDA) antagonist MK-801 (0.1-1 mg/kg, i.p.) injected 30 min before naloxone (3 mg/kg, s.c.) dose-dependently prevented the neurochemical and behavioral signs of morphine withdrawal in guinea pigs and mice. The non-selective antagonist glutamic acid diethylester only at 100 mg/kg i.p. reduced the naloxone-induced increase of cortical acetylcholine release without affecting the behavioral changes. These findings indicate that the activation of excitatory amino acid receptors, mainly the NMDA receptors, plays a relevant role in the expression of opiate abstinence.

Acetylcholine↗
PubMed1991

Influence of acute and chronic chlorimipramine treatment on the 5-HT receptor-mediated modulation of acetylcholine release from the cerebral cortex of freely moving guinea-pigs.

1. Acetylcholine (ACh) release from the cerebral cortex of freely moving guinea-pigs, implanted with epidural cups, was studied. 2. A single dose of chlorimipramine (Cl-Imip, 10 mg kg-1, s.c.), reduced the cortical ACh release both in normal and in chronically (10 mg kg-1 daily, s.c., for 14 days) Cl-Imip-treated guinea-pigs; the 5-HT3 antagonist MDL 72222 (1 mg kg-1, s.c.) antagonized this effect. 3. A single dose of Cl-Imip significantly reduced the effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylaminotetralin) (8-OH-DPAT, 0.1 mg kg-1, s.c.), which nearly doubled the cortical ACh release in control animals. MDL 72222 restored to normal the response to 8-OH-DPAT reduced by the anti-depressant. 4. A single dose of Cl-Imip did not change the inhibitory, MDL 72222-sensitive, effect induced by the 5-HT3 agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT, 500 micrograms, i.c.v.). 5. In chronically Cl-Imip-treated guinea-pigs, the facilitatory effect of 8-OH-DPAT was no longer present, while the inhibitory, MDL 72222-sensitive, effect of 2-methyl-5-HT was maintained. 6. These results indicate that the 5-HT1A receptor-mediated increase in ACh release is reduced by prolonged Cl-Imip treatment, while the 5-HT3 receptor-mediated inhibition of ACh release is unaffected. The relevance of these findings to the antidepressant mechanism of Cl-Imip is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Effect of acute and subchronic nicotine treatment on cortical efflux of [3H]-D-aspartate and endogenous GABA in freely moving guinea-pigs.

1. The [3H]-D-aspartate preloading of the parietal cortex of freely moving guinea-pigs equipped with epidural cups makes it possible to investigate drug effects on the efflux of this radiolabel, assumed as a marker of the glutamatergic structures underlying the cup. In the same model, the efflux of [3H]-gamma-aminobutyric acid ([3H]-GABA) and endogenous GABA can be measured. 2. Nicotine, 0.9-3.6 mg kg-1, s.c., or 3-5 micrograms, i.c.v., increased the efflux of [3H]-D-aspartate but reduced that of GABA. 3. These effects were mediated through mecamylamine-sensitive receptors but the ganglionic blocking agent was devoid of any primary activity. 4. The inhibition of GABA efflux induced by nicotine 3.6 mg kg-1, s.c., was abolished by methysergide 2 mg kg-1, i.p. and was reduced by naloxone 3 mg kg-1, i.p. pretreatment, suggesting the involvement of tryptaminergic and opioid systems. In contrast, muscarinic and catecholamine antagonists were ineffective. 5. Chronic treatment with nicotine (3.6 mg kg-1, twice daily for 16 days) reduced the facilitatory effect of [3H]-D-aspartate and abolished the inhibition of endogenous GABA efflux. 6. A slight increase in the number of nicotinic binding sites (by use of [3H]-nicotine as ligand) was found in the neocortex of chronically treated guinea-pigs. 7. The higher degree of tolerance to chronic nicotine treatment shown by GABA as compared with [3H]-D-aspartate efflux suggests that adaptative changes of the inhibitory neuronal pools prevail. This may contribute to the reinforcing and addictive properties of nicotine.

Acetylcholine↗
PubMed1991

Alpha-2 adrenoreceptor-mediated decrease in gamma-aminobutyric acid outflow in cortical slices and synaptosomes during morphine tolerance.

Morphine tolerance has proven to be accompanied by alterations in the efficiency of many neuronal signals, as well as by an inversion of the noradrenergic signal response of cortical acetylcholine terminals and gamma-aminobutyric acid (GABA) neurons in vivo (decreased acetylcholine and increased GABA release in normal animals, vice versa in tolerant). The latter observation may be relevant in interpreting morphine withdrawal, because the noradrenergic neuron firing rate increases dramatically during its course. This study was designed as an attempt to anatomically localize the inversion of the GABA response to norepinephrine. Because this phenomenon is observed in cortical slices and synaptosomes, it can be postulated that it occurs in the neocortex at the level of the intracortical GABA nerve terminals. Pharmacological analysis demonstrates that although the stimulation observed in controls is alpha-1 adrenoreceptor-mediated, the inhibition in tolerant animals is exerted via alpha-2 adrenoreceptors. Therefore, an increase in number or an improved coupling to the transduction system of alpha-2 adrenoreceptors is hypothesized. This observation gives a clue to a molecular interpretation of the inversion of GABA response to norepinephrine in tolerant animals, which may be of heuristic value in terms of biological interpretation of morphine tolerance.

Animals↗
PubMed1990

Different effects of 8-OH-DPAT, a 5-HT1A receptor agonist, on cortical acetylcholine release, electrocortigram and body temperature in guinea pigs and rats.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose dependently increased cortical acetylcholine (ACh) release and the body temperature of freely moving guinea pigs. Moreover, it evoked an electroencephalographic (EEG) arousal reaction in phenobarbital-pretreated animals. 8-OH-DPAT was about 10 times less effective in increasing cortical ACh release in the rat than in the guinea pig, and did not modify the phenobarbital-synchronized EEG but dose dependently decreased body temperature. The possibility that 5-HT1A receptors play different roles, depending on the animal species, is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Influence of chronic chlorimipramine treatment on the serotonergic modulation of acetylcholine release from guinea pig caudate nucleus slices.

The influence of chronic chlorimipramine (10 mg/kg daily s.c. for 14 days) treatment (CCT) on 5-HT modulation of basal 3H-choline overflow from guinea pig caudate nucleus slices was studied. The increase in basal tritium overflow induced by 5-HT (3-100 mumol/l) or by DOI (30-100 mumol/l) in normal slices was significantly lower in CCT slices. When tetrodotoxin 0.5 mumol/l was added, the facilitatory effect by 5-HT was cancelled, its late inhibitory effect became more evident and to the same extent in normal and CCT slices. This inhibition was cancelled by ICS 205-930 30 mumol/l. These results indicate that the 5-HT2-mediated facilitatory response of intrastriatal cholinergic neurones to 5-HT is reduced by CCT, while the inhibitory response is unaffected.

Acetylcholine↗
PubMed1990

5-HT1A agonists increase and 5-HT3 agonists decrease acetylcholine efflux from the cerebral cortex of freely-moving guinea-pigs.

1. The influence of 5-hydroxytryptamine1A (5-HT1A), 5-HT2 and 5-HT3 agonists and antagonists on acetylcholine (ACh) release from the cerebral cortex was studied in freely moving guinea-pigs. 2. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-1 mg kg-1, s.c.) caused the 5-HT syndrome and dose-dependently increased ACh release. Ru 24969 (1-10 mg kg-1, s.c.) shared the same effects, but it was less potent. (-)-Propranolol (5 mg kg-1) and metitepine (2 mg kg-1) prevented these behavioural and neurochemical responses. 3. (+/-)-1(4-Iodo-2,5-dimethoxyphenyl)2-aminopropane (DOI) up to 2 mg kg-1 did not modify ACh release and ketanserin (0.5 mg kg-1) was ineffective on 5-HT-induced changes of ACh outflow. 4. 2-Methyl-5-HT (500 micrograms, i.c.v.) and 5-HT (500 micrograms, i.c.v.) plus metitepine (2 mg kg-1, s.c.) inhibited the gross behaviour and ACh release. ICS 205-930 (0.5 mg kg-1) prevented these responses. 5. 2-Methyl-5-HT, up to 10 mumols 1(-1), and 8-OH-DPAT, up to 0.1 mumols 1(-1), (like 5-HT) did not change [3H]-choline efflux from cerebral cortex slices. 6. These results suggest that exogenous 5-HT and related selective agonists modulate guinea-pig cortical cholinergic structures through 5-HT1A and 5-HT3 receptors. The stimulation of 5-HT1A autoreceptors may lead to disinhibition of the cholinergic cells, tonically inhibited by the tryptaminergic control. Conversely, the stimulation of 5-HT3 receptors inhibits ACh release, possibly through an interneurone. No direct 5-HT modulation of the cholinergic nerve endings was found.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Pharmacodynamic profile of isbufylline, a new antibronchospastic xanthine devoid of central excitatory actions.

1,3-Dimethyl-7-isobutylxanthine (isbufylline, TE/06; CAS 90162-60-0) is a newly synthetized xanthine derivative. This compound exhibits remarkable antibronchospastic properties both in in vitro and in vivo (after oral or intravenous administration) experimental models. Isbufylline is significantly more effective than theophylline in antagonizing bronchospasms elicited by spasmogens (capsaicin, arachidonic acid, PAF and antigen) which mainly act by a local release of biologically active substances proposed to be involved in the pathogenesis of asthma. Isbufylline, unlike theophylline, possesses little or no CNS excitatory properties. This reduced neuroexcitatory action is probably related to the poor affinity of isbufylline, as compared to theophylline, to A1 purinoceptor. Indeed, isbufylline is ineffective in antagonizing 2Cl-adenosine-induced EEG synchronization. In normotensive and hypertensive rats oral administration of isbufylline resulted in small and transient positive chronotropic and hypotensive response, markedly lower than those elicited by theophylline or enprofylline. Finally isbufylline exhibits phosphodiesterase inhibitory properties, although at concentration 50-100 times higher than those exerting spasmolytic effects in isolated bronchial tissues. As a whole the pharmacodynamic profile of isbufylline is promising and, in the clinical setting, this compound might exert enhanced antiasthma effects coupled to a low incidence of central and cardiovascular adverse effects.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice.

The protection by pyroglutamic acid (CAS 98-79-3) and derivatives Ia-i (injected i.p.) against glutamate- and NMDA (N-methyl-D-aspartate) (i.c.v.) induced seizures in mice has been studied in comparison with known antiepileptics and antagonists of excitatory aminoacids. The potency of pyroglutamic acid and some derivatives (Id,f,g,h) against glutamate-induced convulsions was similar to that shown by glutamic acid diethylester and by valproic acid. Interestingly, pyroglutamic acid did not affect NMDA-induced convulsions which were well antagonized by both 2-amino-5-phosphono valeric acid and by diazepam. Thus, pyroglutamic acid may represent the starting for synthesis of excitatory aminoacid antagonists acting at non NMDA receptors.

Animals↗
PubMed1989

Lack of excitatory amino acid-induced effects on calcium fluxes measured with 45Ca2+ in rat cerebral cortex synaptosomes.

Ca2+ uptake was measured in purified rat cerebral cortex synaptosomes (P3 pellets) using 45Ca2+ as a tracer. Ca2+ influx increased in time, and with an increase in external K+ concentration and temperature. The net (external K+-induced, depolarization-dependent) uptake follows a two-component course. The exponential term, due to the opening of voltage-operated calcium channels (VOC), has a rate constant which increases with an increase in the depolarization level (1.04 versus 0.54 nmol/s/mg protein for 50 mM - versus 15 mM [K+]-dependent net influx). The linear term, due to the Na+/Ca2+ exchange system, has a similar rate constant at all depolarization levels (0.16 +/- 0.05 and 0.11 +/- 0.02 nmol/s/mg protein). Excitatory amino acids (glutamate, kainate and n-methyl-d-aspartate-NMDA-) were tested on this preparation at doses ranging between 5 x 10(-5) M and 5 x 10(-3) M and at multiple incubation times, under resting conditions and under two depolarizing conditions (partial depolarization: 15 mM external K+ and maximal depolarization: 50 mM external K+). NMDA was also tested in the absence of Mg2+. No effect was detectable under any of these experimental conditions. Hypotheses to interpret these data are discussed. Further studies on other preparations are needed in order to directly investigate the presynaptic effects of excitatory amino acids.

Amino Acids↗
PubMed1989

Alpha 1-adrenoreceptor-mediated increase in acetylcholine release in brain slices during morphine tolerance.

Norepinephrine, clonidine, and phenylephrine increased the electrically evoked release of endogenous acetylcholine in cortical slices taken from morphine-tolerant guinea pigs. This effect was alpha 1-adrenoreceptor mediated and was opposite to the alpha 2-adrenoreceptor-mediated inhibition of acetylcholine release, normally elicited by norepinephrine and clonidine. In the presence of prazosin, clonidine recovered its normal inhibitory properties, suggesting that morphine tolerance induced the appearance of an alpha 1-adrenoreceptor-mediated response that overshadowed, but did not cancel, the still present alpha 2-adrenoreceptor inhibitory control. The attempt to prove the presence of alpha-adrenoreceptors on the nerve endings by testing the effect of norepinephrine in synaptosomal preparations (preloaded with [3H]choline and depolarized with KCl and veratridine) was unsuccessful. Therefore the problem of the exact location of this excitatory input remains to be solved. These results confirm previous findings reporting the increase in cortical acetylcholine release induced by the alpha-adrenoreceptor agonists in morphine-tolerant, freely moving guinea pigs and demonstrate that opiate tolerance inverts the direction of the noradrenergic modulation even in the isolated intracortical cholinergic structures.

Acetylcholine↗