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Biomedical subjects

L Beani

Publications and source records attributed to L Beani.

At least 109 records · Page 6Linked to original sources
PubMed1985

The modulation of cortical acetylcholine release by GABA, GABA-like drugs and benzodiazepines in freely moving guinea-pigs.

In order to define the modulatory role played by gamma-aminobutyric acid (GABA) in corticopetal cholinergic projections, the effect of this amino acid and related drugs on gross behaviour, the EEG and the release of acetylcholine (ACh) from the cerebral cortex in freely moving guinea-pigs was studied. gamma Aminobutyric acid, injected intracerebroventricularly (20-50 mumol) induced a three-phase picture: first (5-15 min) behavioural activation and increased release of ACh, then (30-90 min) depression, EEG synchronization and reduced release of ACh, and finally "rebound" stimulation. Ethanolamine-O-sulphate (EOS) injected intraventricularly (28 mumol/kg) or intraperitoneally (14 mmol/kg) reproduced the first two phases of the effects of GABA (i.e. stimulation followed by inhibition), while diazepam (0.7 and 3.5 mumol/kg, i.p.) and flurazepam (32 mumol/kg, i.p.) caused, at first, only depression. Muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridine-3-ol (THIP) injected intraventricularly (in the nmol range) or intraperitoneally (in the mumol range) produced behavioural activation and increased release of ACh; the depressant signs appeared only after very large, toxic doses. Picrotoxin and bicuculline, at sub-convulsive doses, reduced the symptomatology caused by GABA and antagonized the sedation produced by diazepam. Methysergide (8-16 mumol/kg, i.p.) prevented the behavioural activation and the increased release of ACh by GABA, unmasked the depression due to subthreshold doses of diazepam (i.c.v., 7-70 nmol) and reversed the stimulation induced by muscimol into sedation and reduced the outflow of ACh. Pretreatment with 5,7-HT also dampened and shortened the stimulation by muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1985

The effect of morphine on monoamine release and content in guinea-pig brain slices.

The effect of morphine on the efflux of (3H) monoamines as well as the endogenous monoamine contents in electrically stimulated brain slices was investigated. Only at a concentration at high as 30 microM did the drug reduce the tritium efflux and counteracted the monoamine depletion caused by prolonged electrical stimulation. This effect was antagonized by Naloxone 10 microM. Besides the good agreement between the two methods used to evaluate drug effects the discrepancy between morphine concentrations active on the neurosecretory process and those effective in the whole animal is stressed. The opioids may act in vivo either by modulating the firing rate of the monaminergic neurons or by affecting other related neuronal pools.

Animals↗
PubMed1985

Effect of morphine on acetylcholine content of electrically stimulated brain slices.

Acetylcholine (ACh) levels were measured in guinea-pig thalamic and caudatal slices kept at rest or electrically stimulated for different times (2-30 min.). The decrease of ACh content caused by electrical pulses at 1 Hz and 2 Hz in caudate nucleus and thalamus slices, respectively, was directly related to the time of stimulation. The depletion was potentiated by HC-3 10 microM. In this condition the relationship between ACh content and time of stimulation was shifted to the left. In the presence of HC-3, Morphine (Mo) 30 microM did not affect the ACh levels of thalamic and caudatal slices kept at rest. The opioid, on the contrary, reduced the depletion of ACh caused by 10 min stimulation. Naloxone (Nx) 10 microM antagonized the opioid effect in caudate nucleus, while it increased the stimulus-induced ACh depletion in the thalamus treated with Morphine 30 microM. In conclusion, the electrically-stimulated brain tissue perfused with HC-3 may be a suitable tool to study drug effects on ACh depletion. This may offer an indirect, mirror-like evaluation of ACh apparent turnover and release. The results obtained with Mo and Nx support this statement.

Acetylcholine↗
PubMed1984

Different approaches to study acetylcholine release: endogenous ACh versus tritium efflux.

Superfused slices of guinea-pig cerebral cortex (CC), caudate nucleus (CN) and thalamus (Th) were used to compare i) the resting and electrically-evoked release of endogenous acetylcholine (ACh) in the presence of physostigmine (Phys) and ii) the resting and electrically-evoked tritium efflux (after preloading with 3H choline) in the absence or in the presence of Phys and hemicholinium (HC-3). In addition, the effect of GABA, morphine and their antagonists on both effluxes was investigated. By matching the ACh and tritium outflow on a molar basis, an average ratio of 100: 2-4 was found. When expressed as a percentage of tissue content, the ACh release at 2 Hz (2 min) was 4.1 in CN, 0.92 in CC and 0.44 in Th. Lower percent values in the same rank order, were found for tritium outflow with Phys. Thus, CN has the highest secretory activity. Tritium evoked outflow in the presence of Phys was nearly halved in comparison with the normal values (without Phys). Therefore, the autoreceptor-mediated negative feed-back seems to be similar in the three areas. Tritium evoked outflow in the presence of HC-3 was more than doubled in Th (less so in CC and CN) in comparison with the normal values. A second stimulation at 2 Hz (2 min) gave rise to the same outflow in Th while an evident fall in radiolabel efflux was found in CN. Therefore the blockade of high affinity choline uptake plays a different role in Th and CN.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1983

Diazepam antagonizes GABA- and muscimol-induced changes of acetylcholine release in slices of guinea-pig cerebral cortex.

The acetylcholine (ACh) release was studied in superfused, electrically-stimulated slices of guinea-pig cerebral cortex. Muscimol and 4,5,6,7-tetrahydroisoxazolo (5-4-c)-pyridin-3-ol (THIP), as well as exogenous GABA, reduced the electrically-evoked ACh release and enhanced its spontaneous outflow. Picrotoxin antagonized these effects. In addition, picrotoxin and ethanolamine-O-sulphate (EOS) caused opposite changes in transmitter outflow, suggesting the existence of an exogenous GABAergic control on the cholinergic nerve endings. Neither flurazepam 6.6 X 10(-6)--3.3 X10(-5) mol/l nor diazepam 3.3 X 10(-6)--3.3 X 10(-5) mol/l by themselves affected ACh release. Diazepam prevented GABA-, muscimol- and EOS-induced changes in spontaneous and 1 Hz-evoked outflow. Ro 15-1788 3.3 X 10(*-6) mol/l abolished diazepam antagonism vs exogenous GABA. The ineffectiveness of flurazepam and diazepam on normal release (i.e. the lack of potentiation vs the endogenous GABAergic control) supports the view that "synaptic" GABA receptors acting upon the cholinergic nerve endings are not coupled with Benzodiazepine receptors. The unexpected diazepam antagonism vs exogenous GABA and GABA-like compounds can be explained with an unusual Diazepam negative cooperation with "extrasynaptic" GABA receptors, possibly present on the cholinergic terminals. Thus, the rule of benzodiazepine-GABA synergism does not seem always tenable, at least at certain pre-synaptic sites.

Acetylcholine↗
PubMed1983

Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices.

The effect of adenosine on release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution, at rest and during electrical stimulation at frequencies between 0.2 and 20 Hz. Electrical stimulation brought about a linear increase in release of ACh. Adenosine, in concentrations ranging from 1 to 100 microM, reduced in a dose-dependent manner the release of ACh and was more active on the stimulated than on the resting release. However, the fractional reduction by adenosine of stimulated release of ACh did not vary with increasing stimulation rate. Adenosine triphosphate was less active than adenosine in reducing release of ACh. The inhibitory effect of adenosine was antagonized by aminophylline (0.5 mM) and did not occur when the stimulated release of ACh was enhanced by blocking muscarinic autoreceptors with atropine (15 nM). Aminophylline (0.1 and 0.5 mM) itself exerted a biphasic effect on release of ACh, increasing it at rest and during stimulation at low frequencies, and decreasing it at higher stimulation rates. The manipulation of endogenous adenosine concentrations by adding adenosine deaminase or diphyridamole, an inhibitor of adenosine uptake, had little effect on release of ACh. Dipyridamole, (4 microM), only significantly decreased release of ACh at the 20 Hz stimulation rate.

Acetylcholine↗
PubMed1983

Glycine-induced changes in acetylcholine release from guinea-pig brain slices.

The effect of glycine (Gly) on acetylcholine (ACh) release from superfused, resting or electrically-stimulated slices of guinea-pig caudate nucleus (CN), brain stem (BS) and cerebral cortex (CC) was studied. The amino acid 1 X 10(-4)-6 X 10(-3)mol 1(-1) reduced the electrically-induced release and increased the spontaneous and KCl-evoked transmitter outflow, mostly in CN but also in BS, whereas it was ineffective in CC. Taurine, chosen as a structurally related compound, moderately affected only the spontaneous release in CN. Strychnine 2 X 10(-7) mol 1(-1) was per se ineffective, but prevented most Gly effects. The Gly-induced increase of ACh outflow in resting CN slices, however, could be completely antagonized only by administering strychnine and picrotoxin together. These findings suggest that: (i) the overall pattern of Gly influence on cholinergic function is similar to that previously described for gamma-aminobutyric acid (GABA); (ii) specific receptors seem to be present in BS and, above all, in CN; (iii) a positive cooperation between endogenous GABA and Gly is evident in resting CN slices; (iv) the absence of any apparent endogenous glycinergic control on the cholinergic neurones casts doubt on but does not exclude the existence of glycinergic neurones in CN.

Acetylcholine↗
PubMed1983

Modulation of cortical acetylcholine and gamma-aminobutyric acid release in freely moving guinea pigs: effects of clonidine and other adrenergic drugs.

The effects of various doses of clonidine and norepinephrine (NE) on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) from the brain surface of freely moving guinea pigs have been investigated in order to study the role of alpha adrenoceptors on the function of cortical cholinergic and GABAergic neurons. Clonidine administration at doses of 7.5 and 18.7 nmol/kg inhibits by 40% the release of ACh; larger doses (112 nmol/kg) are inactive. On the other hand, the largest dose of clonidine used in this study (112 nmol/kg) increases the release of GABA by 45%, whereas lower doses are inactive. Norepinephrine (0.9 mumol i.c.v.) decreases by 40% the release of ACh and increases by 80% that of GABA. The inhibitory effects of clonidine and of NE on cortical ACh output are completely antagonized by yohimbine (0.28 mumol/kg), a selective alpha-2 antagonist, thus suggesting an involvement of the alpha-2 adrenoceptors in the neurochemical action of the drug. However, yohimbine releases GABA and does not prevent the action of clonidine or of NE on the cortical GABA system. On the other hand, prazosin (35.8 nmol/kg), a selective alpha-1 antagonist, completely antagonizes the stimulating effects of clonidine and of NE on the release of GABA, suggesting that alpha-1 receptors modulate this release. The present experiments indicate that the neurochemical and neuropharmacological profile of activity of clonidine is strictly dependent upon the dose of the drug. In addition, they support the concept that cortical alpha adrenoceptors modulate the function of neurons releasing ACh or GABA.

Acetylcholine↗
PubMed1982

Release of GABA from the guinea-pig neocortex induced by electrical stimulation of the 'locus coeruleus' or by norepinephrine.

GABA release from the cortical surface was measured in freely moving guinea-pigs using collecting cups and a mass-fragmentographic method. Stimulation of the locus coeruleus caused a prolonged sedation of the animals and a 60% increase of GABA output from their cerebral cortex. Similar results were obtained after intraventricular injections of norepinephrine. Phentolamine antagonized these effects. The results suggest that the noradrenergic innervation of the cortex modulates the function of cortical GABA neurons.

Animals↗
PubMed1982

GABA induced changes in acetylcholine release from slices of guinea-pig brain.

The effect of GABA on acetylcholine (ACh) release was investigated on superfused slices of guinea-pig cerebral cortex (CC), caudate nucleus (CN), tuberculum olfactorium and brain stem. GABA (1--6 x 10(-3) mol/l) increased the spontaneous and KCl-evoked ACh overflow in CC and CN, reduced the electrically-evoked release in all areas tested (most evidently in CC and CN) and lowered the threshold of electric stimulation-induced ACh release in CC. These effects were also caused by 3-amino-1-propane sulphonic acid (1 x 10(-3) mol/l) and ethanolamine-O-sulphate (2 x 10(-3) mol/l), were reduced by bicuculline (1 x 10(-4) mol/l) and fully antagonized by picrotoxin (8 x 10(-5) mol/l), but they were not influenced by phentolamine, methysergide, spiroperidol or strychnine. Tetrodotoxin (TTX) (5 x 10(-7) mol/l) blocked the facilitation of spontaneous ACh release by GABA only when the slices were perfused with normal Krebs solution, but not when perfused with a KCl-enriched medium. These results suggest that GABA affects the cholinergic transmitter release through bicuculline- and picrotoxin-sensitive receptors, showing low affinity toward the agonist. Moreover GABA modulation of resting ACh release requires action potentials only in normal [K+]0, but not in high [K+]0, suggesting that GABA-receptive sites are located at cholinergic terminals.

Acetylcholine↗
PubMed1982

The effect of naloxone on opioid-induced inhibition and facilitation of acetylcholine release in brain slices.

1 The effect of morphine, methionine-enkephalin (Met-enkephalin) and D-Ala2-D-Leu5-enkephalin (DADLE) were tested on the spontaneous and electrically-evoked release of acetylcholine (ACh) from superfused slices of guinea-pig thalamus, caudate nucleus and cerebral cortex. 2 At no concentration did morphine, Met-enkephalin or DADLE modify the outflow of ACh at rest but Met-enkephalin in the presence of naloxone, reduced the resting ACh release. 3 Morphine, at a low dose (3 microM) had no effect in slices of cerebral cortex, but it enhanced the evoked release of ACh in thalamic and caudate, slices. At higher doses of morphine (10-30 microM), the ACh release evoked by electrical pulses was significantly inhibited in every area. 4 Met-enkephalin behaved like morphine in thalamic slices, whereas DADLE, a specific delta agonist, produced a slight inhibition of ACh outflow only at 10 microM. 5 Naloxone antagonized the inhibitory effect of morphine in the cerebral cortex and caudate nucleus slices. Naloxone and also spiroperidol blocked the releasing effect of morphine in caudate slices. In contrast naloxone did not affect the increase of ACh release caused by morphine and Met-enkephalin in thalamic slices. The inhibitory effect of both opioids at high doses was reversed by naloxone so that they then enhanced ACh release. 6 A two fold increase of calcium concentration in the Krebs solution prevented the inhibitory effects of morphine 10 microM. 7 It is suggested that two receptors are present in thalamic slices, one of which inhibits and the other facilitates ACh release.

Acetylcholine↗
PubMed1981

The release of gamma-aminobutyric acid, glutamate, and acetylcholine from striatal slices: a mass fragmentographic study.

The release processes of endogenous Acetylcholine (ACh), gamma-aminobutyric acid (GABA), glutamate (Glu) and glutamine (GLN) were studied in superfused guinea-pig caudatal slices. Basal ACh release remained constant for up to 2 h, while the basal release of GABA, Glu and GLN declined to half or less of its initial values after 1 h of superfusion. Electrical stimulation increased the ACh release by 700-800% and that of GABA by 80% whereas it decreased the output of Glu by 50% and failed to modify the GLN efflux. KCl (25 nM) increased the output of ACh by 400%, that of GABA by approximately 500% and decreased that of Glu by 40%. Substituting of CaCl(2) by MgCl(2) in the superfusion medium reduced the basal efflux of GABA, Glu and GLN. Under these conditions, no evoked release of ACh or of GABA was detected, following electrical or KCl stimulation. Tetrodotoxin 5 x 10(-7) decreased the basal ACh release by 60% and increased the GABA efflux by 40%. The toxin abolished the stimulus-evoked ACh efflux but scarcely affected that of GABA. These results are consistent with a possible neurotransmitter role of ACh and GABA in the striatum and show some differences in the ionic mechanisms underlying GABA and ACh release.

Acetylcholine↗
PubMed1981

Changes in synaptosomal high affinity choline uptake following electrical stimulation of guinea-pig cortical slices: effect of atropine and physostigmine.

1 Superfused guinea-pig cortical slices were electrically stimulated at different frequencies and the changes in acetylcholine (ACh) content measured. Synaptosomes were prepared at the end of the stimulation period and high affinity choline uptake (HACU) rate was measured. 2 The effect of increasing KC1 concentrations was compared on ACh content of the slices and on synaptosomal HACU. 3 Electrical stimulation (2, 5, 10, 20 Hz) elicited a frequency-dependent linear increase in synaptosomal HACU rate and a decrease in ACh content of the slices. 4 The addition of atropine (1.5 x 10(-8) M) to the slices enhanced and that of physostigmine (3 x 10(-5) M) reduced the frequency-dependent increase in HACU rate. Atropine (1.5 x 10(-6) M) not only antagonized the effect of physostigmine, but the HACU rate measured after treatment with both drugs was larger than that found after atropine alone. 5 These results indicate that in the cortical cholinergic nerve endings, depolarization caused by electrical stimulation is coupled with an increase in choline transport which can be modulated by the addition of atropine or physostigmine. Furthermore, within given experimental conditions a linear relationship exists between the reciprocal of ACh content in the slices and synaptosomal HACU.

Acetylcholine↗
PubMed1980

Effect of haloperidol and pimozide on acetylcholine output from the cerebral cortex in rats and guinea pigs.

The effect of haloperidol, pimozide and amphetamine on acetylcholine (ACh) output from the cerebral cortex was investigated in unanaesthetized, freely moving and urethane-anaesthetized rats and guinea pigs. Haloperidol (1 mg/kg i.p.) decreased ACh output only in the anaesthetized rats and increased it only in unanaesthetized guinea pigs. Pimozide (1 mg/kg i.p.) stimulated ACh output in unanaesthetized rats and guinea pigs and anaesthetized guinea pigs, but not in anaesthetized rats. Amphetamine (1 mg/kg i.p.) in all cases, stimulated ACh output. In rats with a septal lesion, the effect of amphetamine on ACh output was suppressed but that of pimozide was still present.

Acetylcholine↗
PubMed1979

Dopamine modulation of acetylcholine release from the guinea-pig brain.

The effect of dopamine (DA) and apomorphine (Apo) on acetylcholine (ACh) release from guinea-pig brain was investigated (i) in superfused slices of cerebral cortex, caudate nucleus, tuberculum olfactorium, brain stem and (ii) in unrestrained, unanaesthetized animals, provided with epidural parietal cups. DA reduced the ACh release only from slices of caudate nucleus, whereas Apo was also effective in the cerebral cortex. DA and Apo inhibition in caudate nucleus was antagonized by spiroperidol. The injection of DA (1.5 and 5 micromoles) into the cerebral ventricles (i.c.v.) caused a late, moderate behavioural stimulation and enhanced ACh outflow from the parietal cortex. The injection of Apo, either i.c.v. or i.p., promptly elicited similar effects. Spiroperidol 0.5--2 mg/kg i.p. counteracted the behavioural stimulation by Apo and amphetamine, but unexpectedly enhanced the cortical ACh outflow, leaving unaffected the cholinergic responses to Apo and Amphetamine. These results show that DA directly hinders ACh release from the striatal cholinergic structures surviving in vitro, via classical neuroleptic-sensitive receptors. On the other hand, the enhanced cortical ACh outflow caused by DA and DA-mimetic drugs in the unanaesthetized animals is suggestive of a disinhibition of the corticopetal cholinergic neurones, via neuroleptic-insensitive mechanisms. Hence, the 'paradoxical' effect of spiroperidol might represent the consequence of the increased activity of nigral DA cells with collaterals possibly involved in the control of the ascending cholinergic pathways.

Acetylcholine↗